Endothelial dysfunction (EtD) has emerged as a critical master pathway in the pathogenesis of both vascular disease and erectile dysfunction (ED). Drugs that have been developed for vascular diseases and/or found to have beneficial endothelial effects may be helpful in the management of ED. In this manuscript we summarize the current state of the art with respect to endothelial active drugs and discuss the evidence supporting their use in the management of ED. Pubmed query for the terms Endothelial dysfunction, erectile dysfunction, pharmaceuticals, “endothelium”, “function”, “pharmaceutical”, “eNOS”, “erectile dysfunction” and “erectile function” was conducted. Relevant articles were reviewed and summarized. A variety of cardiovascular medications have mechanisms of action that involve the endothelium. Examples include HMG-CoA Reductase inhibitors (“statins”), Angiotensin Converting Enzyme Inhibitors (ACEI), Angiotensin Receptor blockers (ARB), Endothelin Receptor Antagonists (ERA), certain beta blockers, and some oral hypoglycemics. Some of these drugs have been found to improve penile erection, although an endothelium dependent mechanism has not been conclusively demonstrated in all studies. Drugs that improve endothelial function in the cavernous arteries and the erectile tissues of the corpora cavernosa hold great promise in treating or at least minimizing the vascular damage that contributes to ED. ACEI and ARB appear to hold great promise in this regard, while statins and oral hypoglycemics may play a potentially useful role as adjunctive therapy for ED. Improvements in endothelial function may help reverse ED in some cases, which would be a marked improvement over management with currently available “on demand” ED therapies.