There have been numerous publications on the coagulopathy of cardiopulmonary bypass (CPB). This review provides an introduction to the history and main components of current CPB circuits and summarizes the current knowledge of pathogenesis, prevention, and treatment of the CPB coagulopathy. It encompasses an overview of intra- and postoperative monitoring of coagulation with special emphasis on the near-patient testing, its main complications, and the transfusion support, while taking into account the major changes in the technology used and supportive care provided since its inception.