BACKGROUND: The majority of children, who present with their first episode of nephrotic syndrome, achieve remission with corticosteroid therapy. Children who fail to respond to corticosteroids may be treated with immunosuppressive agents such as cyclophosphamide, chlorambucil or cyclosporin or with non-immunosuppressive agents such as ACE inhibitors. Optimal combinations of these agents with least toxicity remain to be determined. The aims of this systematic review are to assess the benefits and harms of interventions used to treat idiopathic steroid resistant nephrotic syndrome (SRNS) in children. OBJECTIVES: We aimed to evaluate the benefits and harms of all interventions for children with SRNS. SEARCH STRATEGY: Published and unpublished randomised controlled trials (RCTs) were identified from the Cochrane Controlled Trials Register, MEDLINE, EMBASE, reference lists of articles and abstracts from conference proceedings. SELECTION CRITERIA: RCTs and quasi-RCTs were included if they compared different immunosuppressive agents or non-immunosuppressive agents with placebo, prednisone or other agent given orally or parenterally in children aged 3 months to 18 years with SRNS. DATA COLLECTION AND ANALYSIS: Two reviewers independently searched the literature, determined trial eligibility, assessed quality, extracted data and entered it in RevMan. For dichotomous outcomes, results were expressed as relative risk (RR) and 95% confidence intervals (CI). Data were pooled using the random effects model. MAIN RESULTS: Nine RCTs involving 225 children were included. Cyclosporin when compared with placebo or no treatment significantly increased the number of children who achieved complete remission (three trials, 49 children: RR for persistent nephrotic syndrome 0.64, 95% CI, 0.47 to 0.88). There was no significant difference in the number of children who achieved complete remission between oral cyclophosphamide with prednisone and prednisone alone (two trials, 91 children: RR 1.01, 95% CI 0.74 to 1.36), between intravenous cyclophosphamide and oral cyclophosphamide (one study, 11 children: RR 0.09, 95% CI 0.01 to 1.39) and between azathioprine with prednisone and prednisone alone (one trial 31 children: RR 1.01, 95% CI 0.77 to 1.32). No RCTs were identified comparing combination regimens comprising high dose steroids, alkylating agents or cyclosporin with single agents, placebo or no treatment. REVIEWERS' CONCLUSIONS: Further adequately powered and well designed RCTs are needed to confirm the efficacy of cyclosporin and to evaluate other regimens for idiopathic SRNS including high dose steroids with alkylating agents or cyclosporin.