Cardiovascular disease is the leading cause of morbidity and mortality with annual costs of care exceeding 300 billion US dollars. Although screening tools are advocated for many cancers, the use of subclinical disease tests for cardiovascular disease are considered controversial. Health care payers and many governmental agencies apply cost-effectiveness analysis for the evaluation of new technology being considered for routine application in the US and Europe. Cost-effectiveness analysis by definition provides a comparative analysis of clinical and economic outcome data when evaluating new technology in relation to existing modalities. The current report provides a description of the framework upon methods applied in cost-effectiveness analysis as well as available data on the subject of cardiovascular screening, most notably using the evaluation of coronary calcium screening with electron beam tomography. The current report will also present several decision analytic models on the cost of atherosclerotic imaging including the evaluation of serial monitoring for disease progression and the development of cost-effectiveness models employing intermediate outcomes. Based on this review, there is an unfolding body of evidence that explores both the clinical and economic consequences of screening for atherosclerotic diseases. Although further evidence is required from prospectively designed randomized controlled trials, it appears that the current evidence from small series and decision analytic models supports cardiovascular screening of asymptomatic individuals and that the current results reveal enhanced cost effectiveness when compared with the routine evaluation using a Framingham risk assessment.