The formation of steroid resistance in children with nephrotic syndrome (NS) who were initially steroid responsive was described decades ago but has not been studied in sufficient depth. Except for the International Study of Kidney Disease in Children, conducted more than three decades ago, when only cyclophosphamide was available as a second-line agent in steroid-resistant NS, only a handful of small studies have addressed the problem of late steroid resistance (LSR) over the past 40 years. Epidemiology and risk factors for the formation of LSR and differences in outcomes when compared with initial steroid resistance still remain unknown. While multiple second-line treatment choices (calcineurin inhibitors, mycophenolate mofetil, rituximab) exist today, therapeutic approaches to the patients with LSR remain empirical, as no evidence-based data have become available. In the current issue of Pediatric Nephrology , Straatmann et al. report retrospective data on the treatment outcomes for 29 pediatric NS patients with LSR from eight participating centers of the Midwest Pediatric Research Consortium. The authors describe a current pattern of second-line agents used in their cohort and show that the majority of patients (66 %) achieved complete or partial remission after a period of observation for 85 ± 47 months. The authors also describe the data on renal histology. While these data represent an important step forward in our understanding of LSR, further work is needed before firm clinical recommendations can be made. Large-scale prospective studies are required to answer important questions about the epidemiology, genetics and outcomes in late steroid-resistant NS, explore the role of medication adherence and develop evidence-based practice guidelines.