Pediatric liver transplantation is now so successful that we expect more than 80% of children to survive into adolescence and adulthood. As the focus of care shifts toward long-term patient management, immunosuppressive regimens should, in addition to preventing acute and chronic rejection, promote good quality of life and be free of significant long-term side effects. Historically, the most effective immunosuppressive regimens have been based on induction with a combination of calcineurin inhibitors (cyclosporin or tacrolimus) and steroids. Usually, maintenance is monotherapy with cyclosporin or tacrolimus or dual therapy with low-dose alternate-day steroids to encourage growth. A number of studies, including long-term follow-up, have shown significantly lower incidences of rejection, hypertension, hyperlipidemia and cosmetic side effects in patients treated initially with tacrolimus compared with cyclosporin. The use of anti-interleukin-2 inhibitors as induction therapy, with low-dose tacrolimus or in combination with mycophenolate mofetil, has a key role in preventing significant renal dysfunction and reducing infection and rejection. Steroid-free immunosuppression is also proving to be an effective option for the management of pediatric liver recipients. The main challenges now facing pediatricians include ensuring long-term quality of life, optimizing immunosuppression while preventing associated adverse events, and managing a smooth transition from childhood to adolescence and adulthood.