Over the last 20 years cyclosporine (CsA) has improved the survival of kidney, heart, and liver transplants. However, with increasing use, evidence has accumulated that CsA therapy carries a variety of side effects, the most important being renal toxicity. CsA can lead to a wide spectrum of renal function impairments, including a marked and rapidly reversible decrease in renal hemodynamics (acute CsA nephrotoxicity), and a chronic form of renal damage that potentially progress irreversibly to end-stage renal disease (chronic CsA nephrotoxicity). All these manifestations are the consequence of the drug toxic effects on renal vessels and the tubulointerstitium. A proper diagnosis of CsA toxicity at early stages, the combination of low CsA doses with non-nephrotoxic immunosuppressants, and the development of more feasible strategies to monitor daily CsA exposure may contribute to a better CsA management, improve quality of life of transplant recipients, and prolong graft survival.