Mycophenolate mofetil (MMF) has been used in kidney and pancreas transplantation for almost 10 years. In the pivotal phase III trials, MMF use was accompanied by a dramatic reduction of rejection rates in kidney transplantation; however, the impact on graft and patient was undetermined. Analyses of the United States Renal Data System and the Scientific Registry of Transplant Recipients databases later provided a valuable measure of the impact of MMF in improving outcomes. In this review, we provide a synopsis of the prospective studies, including but not limited to the pivotal MMF approval trials, and analyses of the national transplant registries relevant to the long-term impact of MMF in kidney transplantation. Indeed, a substantial body of evidence has shown MMF treatment improves patient survival, graft survival, and death-censored graft survival in kidney transplantation. The beneficial effects of MMF have been particularly notable in high-risk recipients such as African Americans. In coming years, these benefits will require reevaluation in the context of the growing use of novel protocols combining MMF with tacrolimus or sirolimus.