Adverse drug reactions are a concern for all clinicians who utilize medications to treat adults and children; however, the frequency of adult and pediatric adverse drug reactions is likely to be under-reported. In this age of genomics and personalized medicine, identifying genetic variation that results in differences in drug biotransformation and response has contributed to significant advances in the utilization of several commonly used medications in adults. In order to better understand the variability of drug response in children however, we must not only consider differences in genotype, but also variation in gene expression during growth and development, namely ontogeny. In this article, recommendations for systematically approaching pharmacogenomic studies in children are discussed, and several examples of studies that investigate the genomic and developmental contribution to adverse drug reactions in children are reviewed.