Erectile dysfunction (ED) has been defined as the inability to attain or maintain penile erection sufficient for successful sexual intercourse. ED carries a notable influence on life quality, with significant implications for family and social relationships. Because atherosclerosis of penile arteries represents one of the most frequent ED causes, patients presenting with it should always be investigated for potential coexistent coronary or peripheral disease. Up to 75% of ED patients have a stenosis of the iliac-pudendal-penile arteries, supplying the male genital organ’s perfusion. Recently, pathophysiology and molecular basis of male erection have been elucidated, giving the ground to pharmacological and mechanical revascularization treatment of this condition. This review will focus on the normal anatomy and physiology of erection, the pathophysiology of ED, the relation between ED and cardiovascular diseases, and, lastly, on the molecular basis of erectile dysfunction.