The purpose of this article is to evaluate the use of perioperative antithrombotics in patients undergoing surgical revascularization of the coronary vessels. Although there is a general agreement about the use of anticoagulation during off-pump coronary revascularization (OPCAB), the degree of the required anticoagulation varies from one center to another. The review is divided into four major sections. The first section describes the pathophysiology of the coagulation system in cardiac surgery with and without the use of cardiopulmonary bypass. In this section, we also discuss the interactions between the coagulation system and the inflammatory response to cardiac surgery. The second section examines the role of prophylactic antithrombosis in patients referred to surgical revascularization, and their role in bleeding complications associated with surgery. Heparinization and neutralizing its anticoagulative effects during coronary surgery are discussed in the third section. The fourth section examines the evidence that the inflammatory response contributes to adverse peri-operative events, in particular organ dysfunction, and potential therapeutic strategies to control this response. The review concludes with a summary of potential future research directions and key deficiencies in our knowledge regarding the use of anticoagulants in cardiac surgery.