Solid organ pancreas transplantation is a durable treatment for establishing normal blood glucose levels in patients with diabetes. Historically, younger patients with type 1 diabetes have been the primary recipients of pancreas transplants. As surgical techniques and post-operative immunosuppression regimens have continued to improve, indications have expanded such that non-traditional recipients are being evaluated for pancreas transplantation. These recipients include patients with type 2 diabetes, patients older than 50 years of age, and patients with chronic infectious diseases, including HIV and HCV. Despite limited literature in these patient populations, pancreas transplantation is a viable treatment for endocrine pancreas failure in appropriately selected patients, regardless of disease etiology or age. This review summarizes the current literature on pancreas transplantation in non-traditional recipients.