Erectile dysfunction (ED) is a common urologic condition that causes distress in men. Risk factors and predictors for ED include age, cardiovascular disease (CVD), hypertension, diabetes, smoking, and certain medications. CVD and ED share several risk factors, and ED may be a predictor of future cardiovascular events. Lifestyle modifications and phosphodiesterase type 5 inhibitors (PDE5Is) are considered first-line therapies for ED. PDE5Is can be less effective in patients with diabetes and should be used cautiously in certain patients with CVD. This review explores treatment options for ED with a focus on those with a history of diabetes or CVD.