Background Calcineurin inhibitors(CNIs)are commonly given to transplant recipients of kidneys and other solid organs and to patients with immune disorders,such as steroid-resistant nephrotic syndrome,steroid-dependent nephrotic syndrome,and frequent relapse nephrotic syndrome.Although CNIs remain the most effective available immunosuppressant agent,there is clinical concern regarding possible long-term nephrotoxicity.This concern is especially significant in children who have a longer life expectancy and greater growth rate.Data sources In this review,we analyzed the literatures to identify original articles that examined use of CNIs in children who received organ transplantation and nephropathy to assess the available evidence of their nephrotoxicity.PubMed,Elsevier,and Tompson ISI Web of Knowledge were searched for identifying relevant papers.Results Clinical research supports the presence of CNI-related nephrotoxicity.However,some researchers have questioned the prevalence and seriousness of chronic CNIs nephrotoxicity,especially because the pathological lesions typically associ-ated with long-term CNI use are nonspecific.Many researchers have focused on early markers of CNI nephrotoxicity,and the methods that may help prevent and manage nephrotoxicity.Conclusions Future research should focus on investigating early markers of CNI nephrotoxicity and strategies for improved immunosuppressant therapy,and developing alternative treatments.CNI-mediated nephrotoxicity should always be taken seriously in clinic.