Pyoderma gangrenosum (PG) is a non-infectious reactive neutrophilic dermatosis which typically starts with pustules which rapidly evolve to painful ulcers of variable size and depth with undermined violaceous borders. Since its first description in 1930, the pathogenesis of PG has remained elusive even as an ever-widening range of systemic diseases has been described in association with it. The diagnosis of PG is based on clinical and pathologic features and requires exclusion of other conditions that produce ulcerations, since misdiagnosis exposes patients to risks associated with treatment. Critical to proper management are correct diagnosis, identification and treatment of any underlying disorder, and the appropriate choice of topical and systemic therapy. PG has four distinctive clinical and histologic variants, and the specific clinical features of the lesion may provide a clue to the associated disease. The most common associated diseases are inflammatory bowel disease, rheumatological or hematological disease or malignancy. Although there is no single successful treatment for PG, certain type of PG lesions are recognized to respond more readily to accepted therapies than others. Local treatment may be sufficient for mild disease, while systemic immunosuppressive therapy is necessary for severe cases. The treatments with the best clinical evidence are oral or pulse intravenous corticosteroids, and cyclosporine. Surgical therapy is useful in selected cases in conjunction with immunosuppression. Wound stabilization is obtained only through control of the systemic and local inflammatory process. Emerging therapies include use of platelet-derived growth factor and cell culture grafts when re-epithelialization is slow, and the TNF-alpha blocking agent infliximab for refractory disease. Despite advances in therapy, the long-term outcome for patients with PG remains unpredictable, because relapses are common.