Hypertension is a common, complex disease phenotype that has been intensively studied to identify susceptibility loci in humans. Candidate genes continue to be uncovered via genetic analysis in model organisms through linkage analysis with families and/or sib-pairs and through association studies using sequence variants in genes that play a role in key pathways regulating blood pressure in humans, such as the renin-angiotensin system (RAS). Recent studies exploring the sequence diversity in human candidate genes suggest that the distribution and organization of single nucleotide polymorphisms (SNPs) within and among human populations is complex. Issues related to the use of SNPs in analyzing the genetic determinants of hypertension are illustrated using recent studies on the angiotensin-converting enzyme (ACE).