The last several decades have witnessed a substantial decrease in the incidence of acute allograft rejection following kidney transplantation, although commensurate improvements in long-term graft function have not been realized. As a result, the primary focus of new immunosuppressive drug development has expanded to include ease of use and improved side effect profile, including reduced nephrotoxicity, in addition to the more traditional goal of improved short-term outcomes. A number of novel drugs are currently under investigation in Phase I, II, or III clinical trials, primarily to replace the nephrotoxic but highly effective calcineurin inhibitors. Belatacept is a humanized antibody that inhibits T cell costimulation and has shown encouraging results in multiple Phase II and III trials. This article reviews the mechanism of action of belatacept, as well as published and preliminary results of the Phase I–III clinical trials involving this novel immunosuppressive agent.