The early identification of susceptibility to adverse cardiovascular outcomes and risk stratification amongst asymptomatic individuals, as well as amongst those with overt disease continues to be one of the major priorities of clinically-orientated research in the field of atherothrombosis. Available data from epidemiological studies indicate that traditional risk factors do not fully explain the predisposition to cardiovascular disease, its dynamics in different population groups and treatment responses. The pressing need for the development and clinical implementation of new markers of atherothrombotic disease has fuelled rapidly expanding research into cardiac biomarkers. This review outlines the main principles of biomarker qualification that have entered clinical practice, as well as an overview of the development of targeted biomarkers across the cardiovascular “continuum”. We discuss in detail the evidence from epidemiological and clinical studies advocating the potential clinical use of the most promising candidate plasma biomarkers (more specifically, C-reactive protein, coagulation and inflammatory mediators and natriuretic peptides). Such an application of biomarkers to aid clinical risk assessment would be important in our efforts to improve risk stratification of subjects at risk of cardiovascular events.