The Omega-3 Index is defined as the percentage of eicosapentaenoic acid plus docosahexaenoic acid in red blood cell fatty acids, assessed by a standardized methodology. Better than fatty-acid compositions in other compartments, the Omega-3 Index represents a person's status in eicosapentaenoic acid plus docosahexaenoic acid. An Omega-3 Index less than 4% is associated with a tenfold risk for sudden cardiac death in comparison to an Omega-3 Index greater than 8%. Mechanisms of action are plausible and large-scale intervention studies in humans support causality. A low Omega-3 Index may also be a risk factor for coronary artery disease and for complications of congestive heart failure. Ongoing research will define the value of the Omega-3 Index as a risk factor and treatment parameter more precisely.