The widespread use of lipids to define risk has been a success based on the dramatic decrease in the incidence of transmural myocardial infarctions. This success and the fact that many patients with normal lipid levels go on to have acute coronary syndrome have led to investigations on the use of nonlipid-based inflammatory biomarkers to predict risk. Interestingly, as the physiology reflected by distinct biomarkers is better understood, there is increasing interest in multimarker approaches to determine risk and where a given patient may be on a spectrum of risk. In this perspective, we review data from over 95,000 patients who had a multimarker annual wellness panel to demonstrate the utility of multiple markers in defining those patients at risk. We discuss a novel multimarker panel for cardiovascular risk, define the differences between a multimarker approach and expensive amalgamations of multiple markers, and discuss how the field may develop in the future.