Pyoderma gangrenosum (PG) is an uncommon neutrophilic dermatosis consisting of nodules and pustules that ulcerate. Pyoderma gangrenosum is associated with autoimmune disorders such as inflammatory bowel disease, spondyloarthritis, and rheumatoid arthritis. In mild disease, therapy consists of local wound care and topical or intralesional corticosteroids. For more severe disease, systemic agents are necessary. Herein, we present the case of a patient with steroid resistant pyederma gangrenosum associated with ulcerative colitis and ankylosing spondylitis who responded well to infliximab, a tumor necrosis factor blocker. Biological agents (anti-TNF) may be alternative treatment options in patients with resistant PG.