diff --git a/Makefile.inc1 b/Makefile.inc1
--- a/Makefile.inc1
+++ b/Makefile.inc1
@@ -740,6 +740,7 @@
 		MK_CLANG_FULL=no \
 		MK_HTML=no \
 		MK_MAN=no \
+		MK_MSAN=no \
 		MK_PROFILE=no \
 		MK_RETPOLINE=no \
 		MK_SSP=no \
@@ -771,6 +772,7 @@
 		MK_CLANG_FORMAT=no \
 		MK_CLANG_FULL=no \
 		MK_LLDB=no \
+		MK_MSAN=no \
 		MK_RETPOLINE=no \
 		MK_SSP=no \
 		MK_TESTS=no \
@@ -3110,6 +3112,10 @@
 _prereq_libs+=	lib/libclang_rt/asan_cxx
 _prereq_libs+=	lib/libclang_rt/asan_static
 .endif
+.if ${MK_MSAN} != "no"
+_prereq_libs+=	lib/libclang_rt/msan
+_prereq_libs+=	lib/libclang_rt/msan_cxx
+.endif
 .if ${MK_UBSAN} != "no"
 _prereq_libs+=	lib/libclang_rt/ubsan_minimal
 _prereq_libs+=	lib/libclang_rt/ubsan_standalone
diff --git a/Makefile.libcompat b/Makefile.libcompat
--- a/Makefile.libcompat
+++ b/Makefile.libcompat
@@ -69,13 +69,18 @@
 	    -DNO_CPU_CFLAGS \
 	    MK_ASAN=no \
 	    MK_CTF=no \
+	    MK_MSAN=no \
 	    MK_RETPOLINE=no \
 	    MK_SSP=no \
 	    MK_UBSAN=no \
 	    MK_WERROR=no \
 	    _lc_build-tools
 	${_+_}cd ${.CURDIR}; \
-	    ${LIB${_LIBCOMPAT}WMAKE} -f Makefile.inc1 -DNO_FSCHG libraries
+	    ${LIB${_LIBCOMPAT}WMAKE} -f Makefile.inc1 \
+	    -DNO_FSCHG \
+	    MK_ASAN=no \
+	    MK_MSAN=no \
+	    libraries
 
 distribute${libcompat} install${libcompat}: .PHONY
 	${_+_}cd ${.CURDIR}; \
diff --git a/lib/clang/Makefile.inc b/lib/clang/Makefile.inc
--- a/lib/clang/Makefile.inc
+++ b/lib/clang/Makefile.inc
@@ -1,8 +1,14 @@
-
 .include <src.opts.mk>
 
 PACKAGE=	clang
+
+.if ${MK_MSAN} == "yes"
+# Build only PIE static libraries; bsd.lib.mk does not support this directly.
+CFLAGS+=	${PIEFLAG} ${SHARED_CFLAGS}
+CXXFLAGS+=	${PIEFLAG} ${SHARED_CXXFLAGS}
+.else
 MK_PIE:=	no	# Explicit libXXX.a references
+.endif
 
 .if ${MK_LLVM_FULL_DEBUGINFO} == "no"
 .if ${COMPILER_TYPE} == "clang"
diff --git a/lib/csu/Makefile.inc b/lib/csu/Makefile.inc
--- a/lib/csu/Makefile.inc
+++ b/lib/csu/Makefile.inc
@@ -3,6 +3,7 @@
 NO_WMISSING_VARIABLE_DECLARATIONS=
 # Can't instrument these files since that breaks non-sanitized programs.
 MK_ASAN:=	no
+MK_MSAN:=	no
 MK_UBSAN:=	no
 
 .include <src.opts.mk>
diff --git a/lib/csu/tests/Makefile b/lib/csu/tests/Makefile
--- a/lib/csu/tests/Makefile
+++ b/lib/csu/tests/Makefile
@@ -1,9 +1,15 @@
+.include <src.opts.mk>
 
 SUBDIR=		dso
+
+.if ${MK_MSAN} != "yes"
 TESTS_SUBDIRS=	dynamic
+.endif
 TESTS_SUBDIRS+=	dynamiclib
 TESTS_SUBDIRS+=	dynamicpie
+.if ${MK_MSAN} != "yes"
 TESTS_SUBDIRS+=	static
+.endif
 
 SUBDIR_DEPEND_dynamiclib=dso
 
diff --git a/lib/csu/tests/Makefile.tests b/lib/csu/tests/Makefile.tests
--- a/lib/csu/tests/Makefile.tests
+++ b/lib/csu/tests/Makefile.tests
@@ -1,4 +1,3 @@
-
 ATF_TESTS_C+=	init_test
 ATF_TESTS_C+=	fini_test
 ATF_TESTS_CXX+=	cxx_constructors
diff --git a/lib/libc/amd64/string/Makefile.inc b/lib/libc/amd64/string/Makefile.inc
--- a/lib/libc/amd64/string/Makefile.inc
+++ b/lib/libc/amd64/string/Makefile.inc
@@ -34,3 +34,8 @@
 # sanitizer runtime can initialize itself.
 CFLAGS.amd64_archlevel.c+=	-fno-sanitize=address
 .endif
+.if ${MK_MSAN} != "no"
+# Disable MSAN for amd64_archlevel.c since its code is executed before the
+# sanitizer runtime can initialize itself.
+CFLAGS.amd64_archlevel.c+=	-fno-sanitize=memory
+.endif
diff --git a/lib/libc/stdlib/Makefile.inc b/lib/libc/stdlib/Makefile.inc
--- a/lib/libc/stdlib/Makefile.inc
+++ b/lib/libc/stdlib/Makefile.inc
@@ -18,6 +18,9 @@
 
 CFLAGS.qsort.c+= -Wsign-compare
 
+# The MSan runtime calls cxa_atexit() before it has fully initialized itself.
+CFLAGS.atexit.c+= -fno-sanitize=memory
+
 # Work around an issue on case-insensitive file systems.
 # libc has both _Exit.c and _exit.s and they both yield
 # _exit.o (case insensitively speaking).
diff --git a/lib/libclang_rt/Makefile.inc b/lib/libclang_rt/Makefile.inc
--- a/lib/libclang_rt/Makefile.inc
+++ b/lib/libclang_rt/Makefile.inc
@@ -13,6 +13,7 @@
 NO_PIC=
 MK_PROFILE=	no
 MK_ASAN:=	no
+MK_MSAN:=	no
 MK_SSP=		no
 MK_UBSAN:=	no
 
diff --git a/lib/libgcc_s/Makefile b/lib/libgcc_s/Makefile
--- a/lib/libgcc_s/Makefile
+++ b/lib/libgcc_s/Makefile
@@ -8,6 +8,8 @@
 
 .include <bsd.opts.mk>
 
+# The MSan runtime depends on this library; don't instrument it.
+MK_MSAN=	no
 MK_SSP=		no
 WARNS?=	2
 
diff --git a/lib/libsys/x86/Makefile.sys b/lib/libsys/x86/Makefile.sys
--- a/lib/libsys/x86/Makefile.sys
+++ b/lib/libsys/x86/Makefile.sys
@@ -19,6 +19,9 @@
 .if ${MK_ASAN} != "no"
 CFLAGS.__vdso_gettc.c+=-fno-sanitize=address
 .endif
+.if ${MK_MSAN} != "no"
+CFLAGS.__vdso_gettc.c+=-fno-sanitize=memory
+.endif
 .if ${MK_UBSAN} != "no"
 CFLAGS.__vdso_gettc.c+=-fno-sanitize=undefined
 .endif
diff --git a/lib/libthr/Makefile b/lib/libthr/Makefile
--- a/lib/libthr/Makefile
+++ b/lib/libthr/Makefile
@@ -15,6 +15,10 @@
 .endif
 
 .include <src.opts.mk>
+
+# _libpthread_init() cannot be instrumented yet.  For instance, rtprio_thread()
+# is not intercepted, so _thr_getscheduler() triggers MSan warnings.
+MK_MSAN=	no
 MK_SSP=	no
 
 LIB=thr
diff --git a/lib/libutil/tests/Makefile b/lib/libutil/tests/Makefile
--- a/lib/libutil/tests/Makefile
+++ b/lib/libutil/tests/Makefile
@@ -1,10 +1,16 @@
+.include <src.opts.mk>
 
 TAP_TESTS_C+=	flopen_test
 TAP_TESTS_C+=	grp_test
 TAP_TESTS_C+=	humanize_number_test
 TAP_TESTS_C+=	pidfile_test
+.if ${MK_MSAN} == "no"
+# These tests define a gethostname() symbol, which collides with the one
+# provided by the sanitizer runtime and thus results in a link error.
+# We cannot simply disable MSAN because libatf.so etc. may be instrumented.
 TAP_TESTS_C+=	trimdomain_test
 TAP_TESTS_C+=	trimdomain-nodomain_test
+.endif
 ATF_TESTS_C+=	cpuset_test
 ATF_TESTS_C+=	expand_number_test
 ATF_TESTS_C+=	forkpty_test
diff --git a/libexec/rtld-elf/Makefile b/libexec/rtld-elf/Makefile
--- a/libexec/rtld-elf/Makefile
+++ b/libexec/rtld-elf/Makefile
@@ -10,6 +10,7 @@
 MK_PIE=		no # Always position independent using local rules
 # Not compatible with sanitizer instrumentation or SSP.
 MK_ASAN=	no
+MK_MSAN=	no
 MK_SSP=		no
 MK_UBSAN=	no
 
diff --git a/share/mk/bsd.opts.mk b/share/mk/bsd.opts.mk
--- a/share/mk/bsd.opts.mk
+++ b/share/mk/bsd.opts.mk
@@ -77,6 +77,7 @@
     CCACHE_BUILD \
     CTF \
     INSTALL_AS_USER \
+    MSAN \
     PROFILE \
     RETPOLINE \
     STALE_STAGED \
diff --git a/share/mk/bsd.progs.mk b/share/mk/bsd.progs.mk
--- a/share/mk/bsd.progs.mk
+++ b/share/mk/bsd.progs.mk
@@ -22,7 +22,8 @@
 .if defined(PROG)
 # just one of many
 PROG_OVERRIDE_VARS +=	BINDIR BINGRP BINOWN BINMODE CSTD CXXSTD DPSRCS MAN \
-			NO_SHARED MK_WERROR PROGNAME STRIP WARNS MK_ASAN MK_UBSAN
+			NO_SHARED MK_WERROR PROGNAME STRIP WARNS \
+			MK_ASAN MK_MSAN MK_UBSAN
 PROG_VARS +=	SRCS CFLAGS CXXFLAGS DEBUG_FLAGS DPADD INTERNALPROG LDADD \
 		LIBADD LINKS LDFLAGS MLINKS ${PROG_OVERRIDE_VARS}
 .for v in ${PROG_VARS:O:u}
diff --git a/share/mk/bsd.sanitizer.mk b/share/mk/bsd.sanitizer.mk
--- a/share/mk/bsd.sanitizer.mk
+++ b/share/mk/bsd.sanitizer.mk
@@ -11,6 +11,17 @@
 _use_sanitizers=	yes
 .endif # ${MK_ASAN} == "yes"
 
+.if ${MK_MSAN} == "yes" && ${NO_SHARED:Uno:tl} == "no"
+.if ${MK_PIE} == "yes"
+SANITIZER_CFLAGS+=	-fsanitize=memory -fsanitize-memory-track-origins -fPIC
+# -fsanitize-memory-param-retval can raise false positives.
+SANITIZER_CFLAGS+=	-fno-sanitize-memory-param-retval
+_use_sanitizers=	yes
+.else
+.warning MSan is only supported for PIE executables
+.endif
+.endif
+
 .if ${MK_UBSAN} == "yes" && ${NO_SHARED:Uno:tl} == "no"
 # Unlike the other sanitizers, UBSan could also work for static libraries.
 # However, this currently results in linker errors (even with the
diff --git a/share/mk/src.opts.mk b/share/mk/src.opts.mk
--- a/share/mk/src.opts.mk
+++ b/share/mk/src.opts.mk
@@ -480,8 +480,8 @@
 MK_LLVM_COV:= no
 .endif
 
-.if ${MK_ASAN} == "yes"
-# In order to get sensible backtraces from ASAN we have to install
+.if ${MK_ASAN} == "yes" || ${MK_MSAN} == "yes"
+# In order to get sensible backtraces from (A|M)SAN we have to install
 # llvm-symbolizer as /usr/bin/addr2line instead of the elftoolchain version.
 MK_LLVM_BINUTILS:=	yes
 .endif
diff --git a/tests/sys/audit/Makefile b/tests/sys/audit/Makefile
--- a/tests/sys/audit/Makefile
+++ b/tests/sys/audit/Makefile
@@ -1,3 +1,8 @@
+.include <src.opts.mk>
+
+# XXX-MJ these tests cannot be built with MSAN enabled so long as
+# libprivateauditd.a is not position-independent.
+.if ${MK_MSAN} != "yes"
 
 TESTSDIR=	${TESTSBASE}/sys/audit
 
@@ -64,4 +69,6 @@
 
 CFLAGS.process-control.c+=	-I${SRCTOP}/tests
 
+.endif # ${MK_MSAN} != "yes"
+
 .include <bsd.test.mk>
diff --git a/tests/sys/capsicum/Makefile b/tests/sys/capsicum/Makefile
--- a/tests/sys/capsicum/Makefile
+++ b/tests/sys/capsicum/Makefile
@@ -43,11 +43,14 @@
 NO_SHARED.$p=
 SRCS.$p=	mini-me.c
 .endfor
-.if ${MK_ASAN} != "no" || ${MK_UBSAN} != "no"
+.if ${MK_ASAN} != "no" || ${MK_MSAN} != "no" || ${MK_UBSAN} != "no"
 # mini-me.o is linked into a static binary so we can't use sanitizers.
 # Note: We have to set CFLAGS here since it will be built as part of
-# _PROGS_COMMON_OBJS and therefore NO_SHARED.$p does not disable ASAN/UBSAN.
-CFLAGS.mini-me.c+=	-fno-sanitize=address -fno-sanitize=undefined
+# _PROGS_COMMON_OBJS and therefore NO_SHARED.$p does not disable
+# ASAN/MSAN/UBSAN.
+CFLAGS.mini-me.c+=	-fno-sanitize=address \
+			-fno-sanitize=memory \
+			-fno-sanitize=undefined
 .endif
 
 BINDIR=	${TESTSDIR}
diff --git a/tools/build/options/WITH_MSAN b/tools/build/options/WITH_MSAN
new file mode 100644
--- /dev/null
+++ b/tools/build/options/WITH_MSAN
@@ -0,0 +1,4 @@
+Build the base system with Memory Sanitizer (MSan) to detect
+uses of uninitialized variables in C and C++ code.
+Requires that Clang be used as the base system compiler
+and that the runtime support library is available.
diff --git a/usr.bin/clang/Makefile.inc b/usr.bin/clang/Makefile.inc
--- a/usr.bin/clang/Makefile.inc
+++ b/usr.bin/clang/Makefile.inc
@@ -1,7 +1,8 @@
-
 .include <src.opts.mk>
 
+.if ${MK_MSAN} != "yes"
 MK_PIE:=	no	# Explicit libXXX.a references
+.endif
 
 .if ${MK_LLVM_FULL_DEBUGINFO} == "no"
 .if ${COMPILER_TYPE} == "clang"
diff --git a/usr.sbin/rpcbind/tests/Makefile b/usr.sbin/rpcbind/tests/Makefile
--- a/usr.sbin/rpcbind/tests/Makefile
+++ b/usr.sbin/rpcbind/tests/Makefile
@@ -1,6 +1,10 @@
-
 .include <src.opts.mk>
 
+# We cannot build this test at all when MSAN is enabled, due to the getifaddrs()
+# symbol collision and since libatf might have been built with MSAN
+# instrumentation.
+.if ${MK_MSAN} != "yes"
+
 .PATH:	${.CURDIR}/..
 
 ATF_TESTS_C=	addrmerge_test
@@ -21,4 +25,6 @@
 LDFLAGS+=-shared-libasan
 .endif
 
+.endif # MK_MSAN != "yes"
+
 .include <bsd.test.mk>