Pyoderma gangrenosum is an ulcerative skin condition of unknown cause. It is often refractory to treatment, requiring high dosages of immunosuppressive medications. A patient with idiopathic pyoderma gangrenosum was successfully treated with methotrexate and weaned off steroids for the first time in four years. The patient had received multiple skin grafts and failed topical treatment, rifampin, dapsone, azathioprine, and intralesional steroids. She required prednisone 60 mg/day for lesion healing. Methotrexate was given orally, with rapid response, allowing discontinuation of prednisone seven months after beginning therapy. There is evidence of neutrophil dysregulation in pyoderma gangrenosum. Methotrexate has been shown to decrease neutrophil migration and chemotaxis, suggesting a role for its use in pyoderma gangrenosum.