Peyronie's disease (PD) is a wound-healing disorder in which a fibrotic plaque forms in the tunica albuginea layer of the penis. It clinically presents as any combination of penile pain, angulation, and erectile dysfunction. Recent studies indicate that PD has a prevalence of 3%-9% in adult men. Although the exact etiology has not been established, PD likely results from a predisposing genetic susceptibility combined with an inciting event such as microtrauma during intercourse. During the initial acute phase (6-18 months), the condition may progress, stabilize, or regress. For this reason authorities recommend a more conservative treatment approach, with a trial of oral and/or intralesional pharmacotherapy, before surgical reconstruction is considered. Oral therapies most commonly employed include tocopherol (vitamin E) and paraaminobenzoate (Potaba), with colchicine, tamoxifen, propoleum, and acetyl-L-carnitine being used less often. There are a limited number of long-term placebo-controlled studies with these oral agents, and for the most part, studies have failed to show a consistent beneficial effect. Intralesional injection therapy for PD is more commonly used as a first-line therapy. The current standard of care includes injection with interferon-alpha-2b, verapamil, or collagenase. Interferon-alpha-2b, in particular, has been documented in a large, multicenter, placebo-controlled study to show significant benefit over placebo in decreasing penile curvature, plaque size, penile pain, and plaque density. However, intralesional interferon is associated with posttreatment flu-like symptoms unless patients are premedicated with a nonsteroid anti-inflammatory agent. Other available therapies that have not consistently shown efficacy in placebo-controlled studies include corticosteroids, orgotein, radiation, and extracorporeal shockwave therapy. Surgery is considered when men with PD do not respond to conservative or medical therapy for approximately 1 year and cannot perform satisfactory sexual intercourse. Ongoing basic research in PD will likely identify future targets for medical exploitation.