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Erectile dysfunction (ED) is a sensitive indicator of wider arterial insufficiency and an early correlate for the presence of ischemic heart disease. Among patients with coronary artery disease, prevalence reports of ED range from 42% to 75%. The US Food and Drug Administration has approved 3 phosphodiesterase-5 (PDE-5) inhibitors for treatment of male sexual dysfunction: sildenafil, tadalafil, and vardenafil. PDE-5 inhibitors also have cardiovascular effects. They inhibit PDE-5 enzymes in pulmonary vasculature, which causes vasodilation that decreases pulmonary vascular pressure. Sildenafil is approved for treatment of patients with pulmonary hypertension. PDE-5 inhibition with sildenafil improves cardiac output by balancing pulmonary and systemic vasodilation, and augments and prolongs the hemodynamic effects of inhaled nitric oxide in patients with chronic congestive heart failure and pulmonary hypertension. In vivo and in vitro studies are examining the possible beneficial effects of PDE-5 inhibitors in conditions such as myocardial infarction and endothelial dysfunction.