Cardiac surgery with cardiopulmonary bypass (CPB) induces an acute phase reaction that has been implicated in the pathogenesis of several postoperative complications. Recent data indicate that a complex sequence of events leads to the final activation of leukocytes and endothelial cells (EC), which is responsible for cell dysfunction in different organs. Activation of the contact system, endotoxemia, ischemia and reperfusion injury and surgical trauma are all potential triggers of inflammation following CPB. Different pro- and anti-inflammatory mediators (cytokines, adhesion molecules) are involved and their release is mediated by intracellular transcription factors (nuclear factor-kappa B, NF-kappa B). In this review, we examine recent advances in the understanding of the pathophysiology of the CPB-induced acute phase reaction and evaluate the different pharmacological, technical and surgical strategies used to reduce its effects. Emphasis is given to the central role of transcription factor NF-kappa B in the complex mechanism of the inflammatory reaction and to the effects of compounds such as heparin and glycosaminoglycans, phosphodiesterase inhibitors and protease inhibitors whose role as anti-inflammatory agent has only recently been recognized.