Studies investigating the effect of rituximab in children with nephrotic syndrome (NS) due to focal segmental glomerulosclerosis (FSGS) have reported conflicting results, with some concluding that patients may require additional immunosuppressive therapy to achieve and/or maintain long-term remission. We report successful treatment of pediatric FSGS with rituximab infusions, followed by maintenance immunosuppression with mycophenolic acid (MPA) and a calcineurin inhibitor (CNI) in 1 patient with refractory steroid-resistant NS (SRNS), and one with frequently relapsing NS (FRNS). Case 1 is a patient with refractory SRNS due to FSGS. MPA and tacrolimus induced complete remission within 6 months following rituximab treatment. Remission was maintained for over 2 years, and the patient's kidney function and body height also returned to normal ranges within this time. Case 2 is a patient with FRNS due to FSGS, who was treated with rituximab followed by MPA and cyclosporine, which successfully prevented relapses for 18 months, that is, at the end point of the observation. Our case report demonstrates that rituximab and a combination of CNIs and MPA can be effective in achieving complete remission in pediatric refractory SRNS and sustaining remission in pediatric FSGS with FRNS and SRNS for several years. This treatment regimen has the advantage of eliminating the need for long-term high-dose steroid treatments, allowing 1 patient to achieve normal growth and recover from other adverse steroid effects.