The emergency department functions from a unique perspective. Often complex decisions must be made about patient management with incomplete information because of poor patient recall, lack of medical records, and no prior interactions with the patient being treated. Treatment decisions are often made before definitive diagnostic tests are performed and before complete historical information can be obtained. In general, emergency physicians will not prescribe treatment for routine clinical management of erectile dysfunction (ED). Conversely, the outpatient treatment of ED can impact treatment options available to the emergency physician when patients present with signs or symptoms of potential acute coronary syndromes (ACS). The emergency physician needs to have evidence-based guidance on how best to treat patients with potential ACS who are being treated for ED, how much time must elapse between the last dose of phosphodiesterase 5 (PDE5) inhibitor and treatment with nitrates, and how to modify treatment of patients with ACS when patients have recently used a PDE5 inhibitor. Additionally, patients who have been prescribed a PDE5 inhibitor should be educated on the use of nitrates and the need to inform physicians about the use of PDE5 inhibitors during all encounters so that risk can be minimized.