Pyoderma gangrenosum is a noninfectious neutrophilic dermatosis that usually starts with sterile pustules which rapidly progress to painful ulcers of variable depth and size with undermined violaceous borders. In 17 to 74% of cases, pyoderma gangrenosum is associated with an underlying disease, most commonly inflammatory bowel disease, rheumatological or hematological disease or malignancy. Diagnosis of pyoderma gangrenosum is based on a history of an underlying disease, typical clinical presentation and histopathology, and exclusion of other diseases that would lead to a similar appearance. Randomized, double-blinded prospective multicenter trials investigating the treatment of pyoderma gangrenosum are not available. The treatments with the best clinical evidence are systemic corticosteroids (in the initial phase usually 100 to 200 mg/day) and cyclosporine (mainly as a maintenance treatment). Combinations of corticosteroids with cytotoxic drugs such as azathioprine, cyclophosphamide or chlorambucil are used in patients with disease that is resistant to corticosteroids. The combination of corticosteroids with sulfa drugs, such as dapsone, or clofazimine, minocycline and thalidomide, has been used as a corticosteroid-sparing alternative. Limited experience has been documented with methotrexate, colchicine, nicotine, and mycophenolate mofetil, among other drugs. Alternative treatments include local application of granulocyte-macrophage colony-stimulating factor, intravenous immunoglobulins and plasmapheresis. Skin transplants (split-skin grafts or autologous keratinocyte grafts) and the application of bioengineered skin is useful in selected cases in conjunction with immunosuppression. Topical therapy with modern wound dressings is useful to minimize pain and the high risk of secondary infection. The application of topical antibacterials cannot be recommended because of their potential to sensitize and their questionable efficacy, but systemic antibacterial therapy is mandatory when infection is present. Despite recent advances in therapy, the prognosis of pyoderma gangrenosum remains unpredictable.