After more than 20 years of cyclosporine use its nephrotoxicity remains a significant clinical problem. Cyclosporine-induced renal injury has been described in solid organs recipients and in patients treated for autoimmune diseases. It is manifested in 2 distinct and well characterized forms, acute nephrotoxicity and chronic nephrotoxicity. This communication reviews the current literature analyzing the available data about the pathogenesis and mechanisms of acute and chronic cyclosporine-induced nephrotoxicity. A working hypothesis for the possible mechanisms of chronic cyclosporine nephrotoxicity will be provided.