Liver transplantation (LTX) today has become a routine procedure granting curative treatment for various hepatic diseases with excellent survival rates. Constant improvement of immuno-suppressive regimens has led to significant reduction of rejection frequency and increased safety in long-term management. Calcineurin-inhibitors play the key role in most immunosuppressive protocols providing strong T-cell suppression yet often associated with numerous side-effects. Increasing renal insufficiency as well as hypertension, hyperglycaemia, hyperuricaemia, and increased risk of secondary malignancy account for the major problems in short- and long-term follow-up of LTX patients. Mycophenolate mofetil (MMF) as a purine-synthesis inhibitor has proved to be a potent immunosuppressive agent largely free of the CI-associated side-effects. MMF therefore has been used to modulate immunosuppressive protocols in order to both increase efficacy and to reduce CI-related side-effects such as nephrotoxicity. In recent years, MMF-monotherapy protocols have been suggested for LTX patients with renal insufficiency. This review provides an overview on the current role of MMF in immunosuppressive protocols after LTX and evaluates innovative therapeutic concepts.