Our recent understanding of acute coronary syndrome as an atherothrombotic process has led to research efforts in the development of markers of thrombosis and fibrinolysis for risk prediction in cardiovascular heart disease. Although American Heart Association/American College of Cardiology guidelines recommend fibrinogen as a category I risk factor and also suggest factor VII, plasminogen activator inhibitor-1, tissue-type plasminogen activator, and von Willebrand factor as other potentially clinically useful markers, these tests have not come into routine clinical use. Their development as predictors of risk may be hampered by inconsistent laboratory methodology, which causes difficulty in comparing result interpretation with published trial studies. This article presents the history of development for these tests, proper laboratory handling, the best trial data that present evidence of their accuracy, and current guidelines for clinical use.