Erectile dysfunction (ED) and coronary artery disease (CAD) interact in complex ways: ED is increasingly recognized as a harbinger or risk factor for CAD; a small proportion of cases (about 1%) of acute coronary syndromes (ACS), including acute myocardial infarction and sudden cardiac death, occur during or after sexual activity; the absolute risk associated with coitus, including that associated with the use of phosphodiesterase 5 (PDE5) inhibitors to treat ED, is extremely low; virtually all patients experiencing ACS have previously existing (but usually undiagnosed) CAD; and patients often have ED after ACS as a result of psychological factors or drugs, such as β-blockers, used to treat CAD. The Princeton Guidelines provide a pragmatic approach to stratifying the risk of ACS in patients with established CAD or at high risk for future ACS. Only a minority of patients destined to experience ACS, including those events related to coitus, have established CAD. Yet, most have ≥2 coronary risk factors. The most pragmatic approach to decreasing the risk of ACS in such individuals is to maximize risk factor control and institute combination pharmacotherapy, including statins. The PDE5 inhibitors ameliorate not only ED but also endothelial cell dysfunction. Research to establish the role for PDE5 inhibitors in the prevention and control of ACS is in its early stages. The recognition that ED is a potential harbinger of underlying CAD and future ACS is an important milestone in the management of ED. Progress in integrating PDE5 inhibitors into clinical practice will depend on the success with which patients with ED are evaluated and aggressively treated for endothelial cell dysfunction.