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Until recently, erectile dysfunction (ED) was treated by either sexual counseling or penile prosthesis implantation. The advent of intracavernous and transurethral agents has expanded the number of therapeutic options available to ED patients. Furthermore, the approval of oral sildenafil for the treatment of ED in 1998 has prompted an increased awareness of the disease process. With ED now amenable to pharmacologic solutions, research is continuously underway to elucidate the mechanisms underlying the pathophysiologic basis of ED. The hemodynamic changes associated with each erectile event require the integrity of the penile vasculature and neural pathways. Studies that scrutinize the pathophysiology of ED have revealed various modulators or agents that may play a significant role in penile erection. These agents have been demonstrated to mediate their effects through modulation with gap junctions and potassium channels. These findings are facilitated through studies on animal models, specifically aged and diabetes-induced rats. There also appears to be a central control of the cardiac, respiratory, and penile functions that ultimately effects penile tumescence via an intricate cascade of coordinated events. With investigators striving to shed light on the pathophysiologic process of ED, the future does look bright for ED patients as more therapeutic agents, such as new oral agents and gene therapy, are on the horizon.