Pharmacoepidemiology is a relatively new and evolving science that attempts to quantify mainly adverse drug events and patterns of drug use in a large population. The strength of pharmacoepidemiology over randomized trials is the ability to quantify rare adverse events that may occur over long periods. Recently, discordance in the results of pharmacoepidemiologic studies has made it difficult for clinicians and policy makers to make informed drug-therapy decisions. This commentary addresses the strength of pharmacoepidemiology and the advances in the methodology of pharmacoepidemiologic studies over the years. We also discuss the potential problem of discordant results and urge pharmacoepidemiologists to develop good practice guidelines for the conduct of pharmacoepidemiologic studies.