Recent advances in immunosuppressive therapy have dramatically reduced the incidence of acute rejection, thus improving graft survival. As a result, the importance of recurrence of the original nephropathy as a factor affecting the long-term outcome of the graft has grown considerably The incidence of recurrence increases with the increase in graft survival and can currently be estimated between 6 and 15% 10 years after surgery, with great variability among the different histological types of nephropathy. More than 50% of patients with recurrence experience progressive deterioration of graft function, and recurrence of the nephropathy accounts for long-term graft failure in more than 15% of cases. The original disease should be duly considered in all candidates for renal transplantation to identify patients at higher risk for recurrence and to define those treatment protocols devoted to risk reduction. Finally, the risk of disease recurrence should always be included among the parameters used in evaluating a possible transplantation from living donor.