Mycophenolate mofetil (MMF) has been used in rheumatology for over 20 years. When transformed to the active metabolite of mycophenolic acid, it is a potent, selective, reversible inhibitor of inosine monophosphate dehydrogenase, a key enzyme of de novo purine synthesis, exerting a cytostatic effect on T and B cells. It also induces apoptosis of antigen-activated T cell clones, reduces the production of antibodies to inhibit the expression of adhesion molecules, reducing the influx of leukocytes and monocytes to inflammatory sites, and has anti-fibrotic properties. Although the main branch of medicine that uses MMF is transplantation, rheumatologists experienced in application of this drug confirmed its usefulness in the treatment of connective tissue diseases. In comparison with immunosuppressives available in rheumatology, MMF has a very good safety profile and is well tolerated by patients. Through multi-center, randomized, controlled clinical trials, MMF has become well established in the treatment of lupus nephritis. Conclusions about its effectiveness in other rheumatologic indications are not entirely clear, being derived from small clinical trials, observational studies and case reports. They suggest that MMF may also be used to treat extrarenal symptoms of SLE, interstitial lung disease in the course of SSc (systemic sclerosis), PM/DM (polymyositis/dermatomyositis), and skin lesions in these diseases, myositis and systemic vasculitis. It should be emphasized that MMF has proved effective in many cases complicated by multidrug resistance to immunosuppressive therapy and has allowed a significant reduction of long-term corticotherapy or its withdrawal.