<p>Multiple electronic and administrative databases are available for the study of pediatric infectious diseases. In this review, we identify research questions well suited to investigations using these databases and highlight their advantages, including their relatively low cost, efficiency, and ability to detect rare outcomes. We discuss important limitations, including those inherent in observational study designs and the potential for misclassification of exposures and outcomes, and identify strategies for addressing these limitations. We provide examples of commonly used databases and discuss methodologic considerations in undertaking studies using large databases. Last, we propose a checklist for use in planning or evaluating studies of pediatric infectious diseases that employ electronic databases, and we outline additional practical considerations regarding the cost of and how to access commonly used databases.</p>