Extracorporeal membrane oxygenation (ECMO) is a technique that provides temporary pulmonary and/or cardiac support in the setting of acute respiratory distress syndrome, cardiogenic shock, or post-cardiac arrest. ECMO is a complex therapy that requires close and frequent monitoring of patient hemodynamics, volume status, and drug dosing. In addition to pharmacokinetic changes in the critically ill patient, the use of the ECMO circuit largely increases the volume of distribution, and certain drugs are prone to sequestration within the circuit components. ECMO is also associated with complications including coagulopathy (bleeding and thrombosis), hypervolemia, infection, limb ischemia, renal failure, intracerebral hemorrhage, and stroke. It is important that pharmacists practicing in an ICU understand the nuances of drug dosing in the setting of ECMO and its associated complications.