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Risk stratification for primary prevention of cardiovascular disease is today performed using traditional risk factors such as age, gender, blood pressure, serum cholesterol, smoking habits, and plasma glucose. However, these factors perform poorly in the daily clinic where individual risk prediction is needed. It has been suggested to supplement traditional factors with markers of subclinical organ damage to identify subjects with increased susceptibility for the negative influence from the traditional risk factors. Although many new markers are independently associated with cardiovascular risk, their clinical impact on risk prediction is uncertain. In this chapter the evidence for incremental risk prediction for the most promising markers is reviewed, and it is demonstrated that many new markers provide only modest impact on risk prediction with greatest improvement in intermediate risk groups. However, several aspects are still uncertain and need to be examined in the setting of a randomized study. These include actual net benefit of the use of these new markers in risk stratification after taking into account cost, risk associated with the measurements, and the increased downstream medication and examinations, as well as actual changes in patient and physician behavior and clinical outcome.