Rapamycin represents substantial progress as a maintenance immunosuppressive agent to prevent rejection episodes and to decrease steroid and calcineurin inhibitor (CNI) exposure [1–3]. This drug is commonly administered in combination with mycophenolate mofetil, an inhibitor of inosine monophosphate dehydrogenase, or with azathioprine, a purine antimetabolite. Furthermore, rapamycin is prescribed as a substitute for or in combination with CNI. The macrocyclic lactone rapamycin or sirolimus (RapamuneÕ) and its more polar derivative everolimus (CerticanÕ) exhibit a similar mode of action but a different pharmacokinetic behaviour. Everolimus shows a shorter elimination half-life (30 vs 60 h) and a higher bioavailability [4, 5]. In the absence of concomitant use of CNI, rapamycin was shown repeatedly to spare renal function. To the surprise of the transplant community, evidence for rapamycin-associated nephrotoxicity has been accumulating in the last few years. In line with such observations, Crew et al.[6] describe two patients with thrombotic microangiopathy as a result of rapamycin exposure and suggest potential mechanisms of the disorder in this edition of NDT. Thus, definitely, the question has to be addressed whether nephrotoxicity of rapamycin represents a relevant problem in clinical practice.