This article discusses how cardiac surgery and related pathophysiological conditions can impact the pharmacokinetics and pharmacodynamics of drugs in cardiac critical care patients. Specifically, it summarizes how cardiac surgery can affect drug absorption, distribution, metabolism, and elimination. It also reviews how cardiopulmonary bypass during surgery can impact drug disposition. The article emphasizes that drug dosing regimens may need to be adjusted in critically ill cardiac patients to avoid under or overexposure due to these surgical and physiological alterations. Therapeutic drug monitoring is recommended for some drugs to help guide individualized dosing.