Current tools for cardiovascular disease (CVD) risk assessment in asymptomatic individuals are imperfect. Preventive measures aimed only at individuals deemed high risk by current algorithms neglect large numbers of low-risk and intermediate-risk individuals who are destined to develop CVD and who would benefit from early and aggressive treatment. Natriuretic peptides have the potential both to identify individuals at risk for future cardiovascular events and to help detect subclinical CVD. Choosing the appropriate subpopulation to target for natriuretic peptide testing will help maximize the performance and the cost effectiveness. The combined use of multiple risk markers, including biomarkers, genetic testing, and imaging or other noninvasive measures of risk, offers promise for further refining risk assessment algorithms. Recent studies have highlighted the utility of natriuretic peptides for preoperative risk stratification; however, cost effectiveness and outcomes studies are needed to affirm this and other uses of natriuretic peptides for cardiovascular risk assessment in asymptomatic individuals.