Peyronies disease (PD) is a connective tissue disorder characterized by a fibrous plaque involving the tunica albuginea of the penis. The inelastic fibrous plaque leads to a penile curvature. Several Authors have suggested an immunological genesis of this disease, others have linked PD with Dupuytrens contracture. Signs of this disease are curvature, penile pain, penile deformity, difficulty with coitus, shortening, hinging, narrowing and erectile dysfunction. The natural history of PD and the clinical course can develop from spontaneous resolution of symptoms to progressive penile deformity and impotence. Surgical treatment is indicated when patients fail the conservative medical treatment and however, only in case of disease stabilization with a condition of impossibility of penetration. The medical treatment is indicated in the development stage of PD for at least one year after diagnosis and whenever in case of penile pain. Current non-surgical therapy includes vitamin-E, verapamil, para-aminobenzoate, propoleum, colchicine, carnitine, tamoxifen, interferons, collagenase, hyaluronidase, cortisone, pentoxifylline, superoxide dismutase, iontophoresis, radiation, extracorporeal shock wave therapy (ESWT) and the penile extender. The etiology of this fibrotic disease is not widely known, although in recent years pathophysiological knowledge has evolved and new studies propose the penile trauma as cause of the disease. The penile trauma results in a delamination of the tunica albuginea with a consequent small hematoma, then the process evolves as an inflammation with accumulation of inflammatory cells and production of reactive oxygen species (ROS). In the course of the inflammation, Peyronies disease occurs due to the activation of nuclear factor kappa-B, that induces the production of inducible nitric oxide synthase (iNOS), with an increase of nitric oxide, leading to increased production of peroxynitrite anion. All these processes result in the proliferation of fibroblasts and myo-fibroblasts and excessive production of collagen between the layers of the tunica albuginea (penile plaque). Referring to the current knowledge of inflammatory and oxidative mechanisms of PD, a possible therapeutic strategy is then analyzed.