diff --git a/biology/samtools/Makefile b/biology/samtools/Makefile
index 85603f8c1cc8..496dfc8af2a1 100644
--- a/biology/samtools/Makefile
+++ b/biology/samtools/Makefile
@@ -1,27 +1,27 @@
 PORTNAME=	samtools
-DISTVERSION=	1.17
-PORTREVISION=	1
+DISTVERSION=	1.21
 CATEGORIES=	biology
 
 MAINTAINER=	jwb@FreeBSD.org
 COMMENT=	Tools for manipulating next-generation sequencing data
 WWW=		https://www.htslib.org/
 
 LICENSE=	MIT
 LICENSE_FILE=	${WRKSRC}/LICENSE
 
+BUILD_DEPENDS=	htslib>=1.21:biology/htslib
 LIB_DEPENDS=	libhts.so:biology/htslib
 TEST_DEPENDS=	bash:shells/bash
 
 USES=		autoreconf gmake localbase ncurses perl5 python:env shebangfix
 
 USE_GITHUB=	yes
 
 USE_PERL5=	test
 GNU_CONFIGURE=	yes
 GNU_CONFIGURE_MANPREFIX=	${PREFIX}/share
 SHEBANG_FILES=	misc/*.pl misc/plot-bamstats test/test.pl
 
 TEST_TARGET=	test
 
 .include <bsd.port.mk>
diff --git a/biology/samtools/distinfo b/biology/samtools/distinfo
index 55c01a4de639..867f9408bd11 100644
--- a/biology/samtools/distinfo
+++ b/biology/samtools/distinfo
@@ -1,3 +1,3 @@
-TIMESTAMP = 1677245969
-SHA256 (samtools-samtools-1.17_GH0.tar.gz) = f76ec1880468ecaa5341a7256ae896f2cfb191193dbb683046776fb81e18af49
-SIZE (samtools-samtools-1.17_GH0.tar.gz) = 5459752
+TIMESTAMP = 1727437810
+SHA256 (samtools-samtools-1.21_GH0.tar.gz) = b327b85d3d60771ede370c8bcae0570e7704da39abddfe8e930a85b80aabffac
+SIZE (samtools-samtools-1.21_GH0.tar.gz) = 5682709