The cardiac vasculature and myocardium contain components of the renin-angiotensin system (RAS), which may regulate local growth and cellular function. Alterations in the expression or action of these components, which include angiotensin converting enzyme (ACE), angiotensinogen, and angiotensin II type-1 receptors, may contribute to the development of disease, such as hypertension, left ventricular hypertrophy, myocardial infarction, and end-stage heart failure. ACE is one RAS component found to have genetic variants associated with cardiovascular disease. Molecular variants in any of the RAS components may affect signalling pathways, possibly increasing the risk of heart failure. In addition, variants may exacerbate the deleterious effects of altered RAS expression on cardiac function. Genetic variation in RAS components may affect therapy with ACE inhibitors and receptor-blocking agents. Although at present there is no compelling reason to target molecular variations for treatment, a new era in selective pharmacological therapy for cardiovascular disease may be imminent.