This chapter focuses specifically on the influence of the angiotensin-converting enzyme gene (ACE) on human physical performance that was first studied by Montgomery and colleagues in 1998. ACE is involved in catalyzing the conversion of angiotensin I into a physiologically active peptide, angiotensin II. Angiotensin II is a potent vasopressor and aldosterone-stimulating peptide that regulates blood pressure and fluid–electrolyte balance and is also involved with muscle function. A comprehensive Boolean search was run in PubMed and Scopus from coverage to December 28, 2017 to locate all qualifying systematic reviews, meta-analyses, and primary level trials that examined the influence of ACE polymorphisms on endurance performance and/or endurance exercise health-related outcomes. A long-held notion has been that the ACE I allele is associated with enhanced endurance exercise performance, largely due to greater improvements in VO2max/peak associated with the ACE I allele than the D allele.