Cardiac surgery and cardiopulmonary bypass initiate a systemic inflammatory response largely determined by blood contact with foreign surfaces and the activation of complement. It is generally accepted that cardiopulmonary bypass initiates a whole-body inflammatory reaction. The magnitude of this inflammatory reaction varies, but the persistence of any degree of inflammation may be considered potentially harmful to the cardiac patient. The development of strategies to control the inflammatory response following cardiac surgery is currently the focus of considerable research efforts. Diverse techniques including maintenance of hemodynamic stability, minimization of exposure to cardiopulmonary bypass circuitry, and pharmacologic and immunomodulatory agents have been examined in clinical studies. This article briefly reviews the current concepts of the systemic inflammatory response following cardiac surgery, and the various therapeutic strategies being used to modulate this response.