The past decade has witnessed a dramatic increase in the prevalence of obesity. Comorbidities of obesity include type 2 diabetes mellitus, hypertension, and lipid abnormalities, all of which contribute to cardiovascular disease (CVD) and are associated with endothelial dysfunction. These abnormalities frequently cluster in individuals, and the term metabolic syndrome is now widely used to define this cluster. The syndrome is frequently (although not invariably) associated with insulin resistance and CVD. Diabetes is associated with CVD, which may be asymptomatic in some cases, particularly when associated with autonomic neuropathy. This has implications for guidelines on the evaluation of patients with erectile dysfunction (ED) and CVD. Treatment of ED in men with diabetes has been revolutionized by the introduction of phosphodiesterase 5 inhibitors. However, men with diabetes tend to respond less positively to these agents, at least as currently prescribed. This decreased responsiveness may be related to the severity of endothelial function in patients with diabetes. Additional therapeutic strategies may be needed to overcome this problem.