Fibrinogen is far more important as a risk factor for acute cardiovascular syndromes than generally recognized. Evidence from a recent metaanalysis (including 22 studies of 63,736 subjects and 5,717 events [1] suggests that the risk for myocardial infarction and stroke almost doubles if the fibrinogen level exceeds 3.03 g/l (measured according to Clauss) with an odds ratio of 1.99 and a 95% confidence interval of 1.85-2.13. The predictive value of fibrinogen levels equally applies to men and women, young and old, primary and secondary prevention. Repeated fibrinogen measurements are particularly helpful with emphasis on high risk patients: concentrations of the upper tertile indicate a 92% higher risk of impending acute cardiovascular syndromes, as evidenced by a metaanalysis evaluating five prospective studies with 9,639 participants and 671 events [1]. Together with other risk factors such as hypertension, hypercholesterolemia, or diabetes, the risk of fatal and nonfatal acute cardiovascular syndromes may further increase by 6-12- fold, while fibrinogen remains an independent risk factor for both cardiac and extracardiac atherothrombotic complications, as well as for iatrogenic complications like restenosis following PTCA or stenting. Fibrin(ogen) and his effector thrombin substantially determine the extent and outcome of atherothrombotic complications, because they are the molecules linking the mutually dependent events of atherogenesis, coagulation/fibrinolysis, rheology/vasotonus, and inflammation. Interventional studies on fibrinolytic and defibrinating substances, as well as GpIIb/IIIa-inhibitors for treatment of acute cardiovascular syndromes have confirmed the benefit of fibrinogen reduction and extended the experimental evidence for the relevance of fibrin(ogen) in the pathogenesis of these syndromes. Accordingly, the preventive use of fibrates leading to moderate reductions in plasma cholesterol and fibrinogen diminished significantly the rate of reinfarction. The emerging possibilities from a more than 50% fibrinogen reduction (by studies using H.E.L.P. apheresis) strengthened the therapeutic concept to free the blood from all risk factors-as effective as it can be-in order to achieve an optimal plaque regression, since changes in the blood composition strongly affect the fragility and stability of the atherosclerotic plaques.