Extracorporeal membrane oxygenation (ECMO) is a lifesaving treatment for critically ill patients in cardiac or respiratory failure refractory to conventional treatment. Patients on an ECMO circuit (pump, oxygenator, tubing) require numerous medications including sedatives, analgesics, cardioactive medications, and anticonvulsants. Currently, there are few dosing guidelines to optimize pharmacotherapy in this situation. A systematic review was conducted to describe pharmacokinetics (PK) of medications commonly used during ECMO. MEDLINE, Embase, Cochrane, BIOSIS, PubMed, and Web of Science databases were searched. All articles presenting ex vivo, animal, and human data on the PK of the subject medications in the ECMO circuit were included. Three authors independently examined citation titles and abstracts. Four authors extracted relevant details from included studies into standardized data extraction forms. Methodological quality was assessed using the ClinPK guidelines and the Joanna Briggs Institute Checklist. Forty-four studies examining 30 medications were included, 26 ex vivo studies (mostly adult circuits) and 18 observational studies (mainly neonatal patients). Pharmacokinetics varied depending on the medication’s characteristics, study type, and population. Study quality was variable, limiting the possibility of deriving hard dosing guidelines from this available literature. Further population PK studies are needed to adequately determine dosing guidelines in adults and children requiring ECMO.