A number of pharmacologic interventions are now recommended for the prevention of cardiovascular disease, based on the results of randomized controlled trials. These include antihypertensive drugs, lipid-lowering agents, antiplatelet and anticoagulant drugs, estrogen replacement therapy, beta-blockers, and angiotensin converting enzyme (ACE) inhibitors. It is likely that additional pharmacologic interactions will soon be proven efficacious. Despite the strength of this evidence and the development of clinical guidelines incorporating their use, a surprisingly low proportion of patients are actively treated with these agents. There may be a variety of explanations for this, including barriers at the level of the patient, health care provider, and health care institution. Finally, a number of questions remain as to the optimal combination of interventions, both behavioral and pharmacologic, which will yield maximal reduction in risk. The description of factors which reduce the effectiveness of pharmacologic interventions below the efficacy demonstrated in randomized clinical trials should be a fertile area for epidemiologic and behavioral research.