Noncompliance with therapy is widespread in children, with potentially important implications in clinical practice and the research setting. Compliance with therapy is a critical element in the success of therapy, that is, for an efficacious medication to be effective, it must be taken. Demonstration of patterns of drug adherence and the association between compliance and outcome in clinical practice have been facilitated by the recent introduction of electronic monitoring of medication compliance. Determinants of drug compliance, optimal measurement of compliance, and strategies to improve compliance remain to be further explored in children. Given the prevalence of and the potential consequence of noncompliance, pediatricians must have a high index of suspicion of noncompliance to provide the best possible care to their patients.