This article reviews the clinical aspects and epidemiological links between diabetes mellitus and renal transplantation, and emphasizes areas that warrant further clarification. In particular, we summarize the data for various immunosuppression medications on the risk of new-onset diabetes after transplantation (NODAT). An increased mechanistic understanding of new-onset diabetes might provide new insights into the pathophysiology of this complication after solid organ transplantation. Claims that selecting immunosuppression regimen to minimize the risk of NODAT, nevertheless, are currently not supported by the scientific published work. Intuitively, strategies that aim to change the underlying biology of the disease process of NODAT are desirable; among them, lifestyle modification is currently the most promising in terms of real benefit with the least risk.