The pharmacotherapy of critically ill patients poses numerous challenges to the ICU team. Polypharmacy and alterations in drug disposition are common in the ICU; critically ill patients have limited physiologic reserve to deal with adverse drug events. Careful prescribing, based upon sound pharmacologic principles, decreases the potential for preventable adverse events and maximizes the opportunity for successful therapy. A systematic approach to reporting, analysis, and prevention of errors is a further step in our ultimate goal to provide optimal care for the vulnerable patients whom we support in our ICUs.