Three decades ago renal transplantation had become the accepted therapy for end-stage renal disease in children. Cyclosporine (CsA) was introduced into the majority of clinical immunosuppressive protocols in the 1980s and attained a vital place in the armamentarium of antirejection drugs for children. However, CsA therapy is not without adverse effects, notably posttransplant hypertension, hyperlipidemia, and nephrotoxicity. The cosmetic side effects of CsA, principally hirsutism and gum hyperplasia, are significant and very important to children particularly when drug compliance issues are vital to achieve success. The central role CsA has played to date in the development of successful treatment protocols for children undergoing renal transplantation is explored, including the importance of therapeutic drug level monitoring to optimize clinical outcomes.