The concentration-effect relationship for mycophenolic acid (MPA), and the high variability in MPA concentrations in patients on standard dose mycophenolate mofetil (MMF) therapy, for some centers has provided enough evidence to implement therapeutic drug monitoring (TDM) for MMF in daily practice. Two randomized trials Adaption de Posologie du MMF en Greffe Renale (APOMYGRE) and fixed-dose versus concentration controlled (FDCC) investigated the added benefit of TDM for MMF in renal transplant recipients. The APOMYGRE study showed a significant reduction in the incidence of acute rejection in concentration-controlled patients, while the FDCC study had a negative outcome, despite a similar study design. Although it was expected that these prospective trials would give the final answer to the question of whether or not TDM for MMF would be of benefit, it seems that the studies have not had much impact on patient management. Several trials have shown the importance of early adequate exposure to MPA in the first week after transplantation. As it will be hard to improve MPA exposure with TDM, this early, ongoing study now investigates the use of an increased starting dose. The increased starting dose will avoid underexposure to MPA in higher proportions of patients shortly after transplantation but may result in more toxicity in patients with MPA exposures exceeding the upper threshold of the therapeutic window.