The current predominant location for allo-and auto-transplantation of islets is the liver. Despite the historical success of this site, recent studies have revealed multiple disadvantages. Portal hypertension, portal vein thrombosis, bleeding, low oxygen tension, instant blood mediated inflammatory reaction, inadequate alpha cell function, and delays in neovascularization are factors that continue to drive researchers to explore alternative sites for islet transplantation. Factors of an optimal site include: capacity, transplant efficacy, portal venous drainage, high oxygen tension, and easy retrievability. Sites such as the spleen, kidney, intestinal wall, bone marrow, omentum, and peritoneum, among others, have been evaluated for islet transplant. The various benefits and limitations of these alternate sites are reviewed in this article.