Over the past 10 years, the addition of mycophenolate mofetil (MMF) to combination immunosuppressive regimens in cardiac transplant patients has resulted in significant outcomes benefits. Randomized trials and other studies have demonstrated that the use of MMF is associated with a decreased risk of rejection and improved survival. This article will provide an overview of these trials, as well as those evaluating MMF in renal-sparing regimens and in pediatric cardiac transplant recipients. In addition, emerging evidence demonstrating that MMF may provide long-term benefits in reducing cardiac allograft vasculopathy and those evaluating the role of MMF therapeutic drug monitoring in cardiac transplant recipients will be discussed.