Progress in understanding the pathogenesis and treatment of rheumatologic and glomerular diseases such as systemic lupus erythematosus and particularly lupus nephritis has been closely linked with the development of newer immunosuppressive agents. With improved patient survival following the institution of cyclophosphamide and corticosteroid therapy, longer-term management issues came to the forefront, especially how to decrease adverse effects of the immunosuppressive regimen. Many of the immunosuppressive regimens used in lupus patients were first established as efficacious and safe through their use in solid organ transplantation. Mycophenolate mofetil (MMF) is now widely used in the field of transplantation. Following anecdotal reports describing benefits of MMF in lupus and lupus nephritis patients, small studies and finally large randomized, controlled trials have established the use of MMF in these patients, particularly those with lupus nephritis. MMF use in other rheumatologic and renal diseases has been evaluated in only smaller studies and very few randomized controlled trials. Nevertheless, many studies currently are ongoing with this immunosuppressive agent. This article will review the published data and the experience of two major New York medical centers with the use of MMF in autoimmune and renal diseases.