The prevailing notion in dermatology is that mycophenolate mofetil (MMF) is safer than cyclosporine (CsA), but that CsA has greater efficacy. This literature review evaluates the available long-term safety data of MMF and CsA. Literature in the fields of dermatology, autoimmune disease, and transplantation were retrieved from PubMed. Data regarding immunosuppressive and non-immunosuppressive side effects of MMF and CsA are presented along with available pregnancy safety data. Surprisingly, there is a paucity of data on long-term MMF monotherapy. Transplant data is presented separately due to the concomitant use of other immunosuppressants along with MMF. Trends that can be identified include a less discernable cancer or end-organ damage risk in MMF compared to CsA. However, MMF appears to have a greater risk in pregnancy and increased reports of herpes simplex and zoster infection compared to CsA.