Calcineurin inhibitors (CNIs) are frequent first-line agents in children with steroid-resistant nephrotic syndrome (SRNS). However, limited randomized controlled trial (RCT) data are available comparing CNIs with alternative therapies. Gulati and colleagues report their experience with tacrolimus versus cyclophosphamide in childhood SRNS. Their results establish clear superiority of tacrolimus over cyclophosphamide and give further proof that RCTs in childhood SRNS are both feasible and vital for improving the standard of care.