OBJECTIVE To conduct a systematic review of recent case-control and cohort studies in assessing adverse drug events (ADEs) among pediatric patients aged between 0 and 18 years; to establish strengths and limitations of pharmacoepidemiology when applied in evaluating pediatric drug safety; and to identify areas of pediatric drug safety that may be suitable for future pharmacoepidemiological investigations. METHODS A PubMed search was conducted using a list of keywords representing drugs, adverse drug events, case control and cohort studies, and pediatric population. Selection criteria were used to extract relevant studies published from 1/1 2000 to 7/1 2006. RESULTS Twenty-seven studies met our criteria. Of them, 12 used a prospective cohort design. The others were either case-control (seven) or retrospective cohort (eight) studies, based on the analysis of existing databases. More than half of the studies included more than 500 subjects. Inclusion and exclusion criteria for participants in these studies were generally not very stringent. The subjects closely resembled patients in the real-world settings. The length of study follow-up ranged from 1 day to 40 years. In eight studies, the length of follow-up surpassed 5 years. Potential confounding factors were taken into consideration in all of the studies. But the database-based studies generally failed to control for some important clinical variables such as disease severity. Misclassification of drug exposures also occurred in some of these studies. CONCLUSIONS Despite some limitations, pharmacoepidemiology proves to be useful for assessing ADEs in pediatrics. With appropriate study design, this methodology can bolster our understanding about the safety of pediatric drug use. Several areas of pediatric drug safety may especially be suitable for future pharmacoepidemiological investigations. These areas include the safety of polypharmacy, long-term drug effects, and off-label drug use.