The use of therapeutic agents represents a trade-off between the benefits of symptom relief or disease modification that increase quality or length of life and the risk of short- and long-term adverse effects. While evidence suggests that complex medication combinations greatly increase the odds of incurring an adverse drug event,1-3 US Food and Drug Administration approval generally only requires testing of agents in isolation. As a consequence, we often do not know the net health outcomes associated with diverse and intense medication combinations. This uncertainty is magnified in the care of children for whom efficacy and safety studies are often lacking. Despite this therapeutic uncertainty, pediatric drug use is growing.4 A study in this issue of the Archives5 provides a critical examination of the drug exposure of pediatric inpatients. Polypharmacy is the norm for hospitalized infants and children. Should we be concerned?