Peyronie's disease is an acquired condition that presents clinically with a palpable induration, a distinct plaque, or a curvature of the erect penis. At times, the erections are painful. Erectile dysfunction (ED) often is associated with Peyronie's disease. The current era of phosphodiesterase therapy for the treatment of ED seems to have increased the number of patients presenting for treatment of Peyronie's disease. During the past decade, significant advances have been made in understanding the pathophysiology of the disease, resulting in numerous nonsurgical therapies proposed for the treatment of Peyronie's disease. These medical treatments can be administered systemically, locally, or intralesionally. Unfortunately, there are few randomized, placebo-controlled trials to evaluate most of these proposed therapies. In evaluating therapies for Peyronie's disease, it must be remembered that the natural disease history includes spontaneous resolution of pain and even a small improvement in penile curvature in some men. This article reviews the natural history, scientific understanding, and nonsurgical treatment options for the mild to moderate Peyronie's deformities. Surgical therapy remains the mainstay of treatment for severe and refractory cases of Peyronie's disease that result in a physical or psychologic dysfunction.