Tacrolimus is a drug for which therapeutic drug monitoring is recommended. The existence of a wide variety of potential drug interactions further supports the current strategy of measuring whole blood tacrolimus concentrations in transplanted patients. Cytochrome P450 (CYP)3A, the major phase I metabolising enzyme in humans, and the multi-drug efflux pump, P-glycoprotein, are present at high levels in the villus tip of enterocytes in the gastrointestinal tract. Oral bioavailability of tacrolimus can be increased by concomitant administration of inhibitors of either CYP3A or P-glycoprotein. CYP activity in the liver also influences tacrolimus concentrations. As a result, several drugs that are frequently being used in transplantation, such as corticosteroids and antifungal agents, will affect tacrolimus concentrations. Knowledge of such drug interactions is extremely important, as they may lead to clinically important under- or overexposure to tacrolimus, with acute rejection episodes or serious toxicity as a result.