We conclude that HIT II is a serious complication, particularly in patients undergoing cardiovascular surgery that involves CPB. New tests might contribute to the earlier diagnosis of this disease. However, the reduction of immunization by the use of alternative anticoagulants whenever possible seems to be the most effective strategy for the reduction of HIT II-associated complications. If HIT II is diagnosed. r-hirudin is effective as an acute therapy (especially in combination with GP IIb/IIIa inhibitors) and also for further anticoagulation. If patients must undergo CPB, all current alternative anticoagulation concepts are associated with relevant drawbacks that put the patient at an increased risk for post-operative bleeding and/or CPB thrombosis. Currently, r-hirudin is most probably the best option for this purpose. However, when there is impaired renal function, the persistent anticoagulant effect is associated with hemorrhage. Further studies must evaluate whether extracorporeal elimination procedures, such as hemofiltration or plasmapheresis, are effective in avoiding such complications. Otherwise, the combination of UFH with a potent antiplatelet agent, especially with short-acting GP IIb/IIIa antagonists, is an attractive alternative.