The pediatric transplant community stands at a time of unprecedented choice of immunosuppressive agents - and with a legacy of morbidity from those agents used in the previous two decades. This review considers the clinical utility and side-effect profiles of immunosuppressants used widely in current practice (e.g., glucocorticoids, azathioprine, ciclosporin, tacrolimus, mycophenolate, and sirolimus) and those agents which are in increasing use or in evaluation (e.g., IL-2 receptor antibodies, everolimus, FTY720, LEA29Y, and deoxyspergualin). Further consideration is given to the wider drug interactions likely during the use of new immunosuppressant regimens and to our growing awareness of the influences of genetic heterogeneity on drug efficacy and handling. Finally, we consider the new demands being placed on the use of drug monitoring to regulate dosage of this new repertoire of immunosuppressants.