Mycophenolate mofetil (MMF) has conventionally been administered at a fixed dose without routinely monitoring blood levels of mycophenolic acid (MPA), the active metabolite. The contribution of therapeutic drug monitoring (TDM) during MMF therapy remains controversial. A literature review was performed to explore the usefulness of TDM for MPA in solid organ transplantation. In addition, emphasis was placed on the potential clinical benefits and limitations of TDM for MPA. Available studies have limitations and report conflicting results. Although early after transplantation MPA area under the curve might have predictive value for the risk of acute rejection, predose levels appear less reliable. With regard to MPA toxicity, most studies showed no correlation between MPA pharmacokinetics and adverse effects. TDM is hampered by several factors such as the considerable intra-subject variability of MPA pharmacokinetics and the increasing number of different drug combinations. Proposed target ranges are restricted to the early posttransplant period when MMF is used in combination with cyclosporine. The current review of the literature indicates no clear support for a substantial clinical benefit of TDM and more data from prospective randomized trials are needed.