There is an increasing body of literature suggesting the efficacy and tolerability of mycophenolate mofetil (MMF) for the treatment of lupus nephritis. The rationale for its use is based upon its successful profile as an immunosuppressive agent for prevention of allograft rejection, as well as studies in murine models of lupus which have reported improved renal function and animal survival compared to placebo. This report reviews the data regarding MMF therapy in murine lupus models, and describes the initial anecdotal experience with MMF in human lupus, especially in patients with glomerulonephritis who were unresponsive to corticosteroids and cyclophosphamide, or who had unacceptable toxicity on this standard of care regimen. The results of several nonblinded, controlled clinical trials are also described, in which MMF was compared to intravenous or oral cyclophosphamide in patients with lupus nephritis. MMF was found to be well tolerated, with most studies showing fewer infections than that associated with cyclophosphamide. Efficacy of MMF was at least equivalent to cyclophosphamide, and therefore appears to provide an alternative as a standard of care for induction and maintenance treatment of lupus nephritis.