Although statistically and clinically significant, reductions of clinical events seen in large scale intervention studies with omega-3 fatty acids in the cardiovascular field were smaller than would have been predicted from the results of epidemiologic studies. In epidemiologic studies, assessment of intake of fish or eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) predicted clinical events less well than assessing blood levels of EPA and DHA, e.g. by the Omega-3 Index. The Omega-3 Index is the percentage of EPA+DHA in red cell lipids, determined with a highly standardized methodology. Using the perspective of the Omega-3 Index facilitates reconciling discrepancies in results from intervention studies and from epidemiologic studies. Moreover, a low Omega-3 Index can be considered a risk factor for sudden cardiac death and for non-fatal cardiovascular events, whereas a high Omega-3 Index can be used as a therapeutic target. Currently ongoing and future scientific work on the basis of the Omega-3 Index will further define its value.