Penile erection is dependent upon vascular smooth muscle relaxation in erectile tissue and penile arteries, the principal mediator of relaxation being nitric oxide (NO). Evidence from basic scientific studies indicates that oxidative stress mediated through the superoxide radical (superoxide) and other reactive oxygen species (ROS) may be central to impaired cavernosal function in erectile dysfunction (ED). Increased inactivation of NO by superoxide results in impaired penile NO transmission and smooth muscle relaxation. Furthermore, propagation of endothelial dysfunction by ROS may result in chronic impairment of penile vascular function, a process analogous to early atherogenesis. Indeed, ED and atherosclerosis are closely linked through shared risk factors. Given our current understanding of ED pathophysiology, antioxidants may be of benefit in both the short- and long-term. Evidence supporting the paradigm of antioxidant therapy for the prevention or treatment of ED is presented herein.