The use of cardiopulmonary bypass for surgical cardiac procedures is characterized by a whole-body inflammatory reaction due to the contact of blood through nonendothelialized surfaces; this stimulates the organism to recognize the cardiopulmonary bypass system as "nonself" and to activate specific (immune) and nonspecific (inflammatory) responses. These responses are then related with postoperative damage to many body systems, like pulmonary, renal or brain dysfunction, excessive bleeding and postoperative sepsis. In this paper, present knowledge on untoward responses of the patient to the use of cardiopulmonary bypass in cardiac surgery is reviewed and discussed, particularly focusing on the perturbation of the hemostasis and of the complement activation system.