Blood levels of omega-3 fatty acids reflect the interplay of metabolism and the intake of omega-3-rich foods (eg, oily fish). Multiple lines of evidence link reduced tissue and/or blood levels of omega-3 fatty acids, as reflected in the erythrocyte eicosapentaenoic acid plus docosahexaenoic acid level (ie, the omega-3 index), with increased risk for coronary heart disease, especially sudden cardiac death. The purpose of this review is to examine the extent to which biomarkers like the omega-3 index qualify as coronary heart disease risk markers and/or risk factors based on new criteria from the American Heart Association and older guidelines proposed in 1965 by Sir Austin Bradford Hill. These standards include consistency, strength of association, biological plausibility, coherence, dose-response relationship, clinical utility, cost effectiveness, and prospective validation. The omega-3 index appears to fulfill many of the requirements for a risk marker and, more importantly, for a risk factor.