Pyoderma gangrenosum (PG) is an uncommon inflammatory neutrophilic disorder with a spectrum of clinical presentations with variable courses. Most cases are associated with an autoimmune disorder and manifest in middle-aged adults as a painful lesion that progresses to painful necrotizing ulcers of the lower extremity. Owing to its variability, clinical diagnosis remains difficult and many patients are often misdiagnosed, with resulting delay in treatment. While early immunosuppressant therapy is key to preventing progression of PG, surgical treatment has been met with criticism because of the risk of potentiating pathergy, an exaggerated skin reaction due to trauma. This article presents a case series in which 3 patients with PG lesions underwent different treatment methods, including surgical debridement and use of fetal bovine dermis (FBD). The use of FBD in conjunction with medical treatment provided pain relief and wound coverage as well as encouraged growth of granulation tissue and long-term stability. Commercial cellular and tissue-based products used to aid in accelerating PG wound closure are also reviewed.