It is often challenging to explain to potential transplant recipients that the mainstay of their immunosuppressive regimen is lifelong therapy with a calcineurin inhibitor (CNI). Despite careful monitoring of drug levels, these agents are nephrotoxic, reduce kidney transplant function, and for a small number of nonkidney transplant recipients, may even lead to kidney failure requiring dialysis or transplantation. Moreover, the available CNIs have a range of other side effects (hypertension, new-onset diabetes mellitus, dyslipidemia, neurotoxicity, and cosmetic effects) and may contribute to the increased risk for cardiovascular (CV) disease following transplantation.