•Polyunsaturated fatty acid blood levels have predictive power for disease outcomes.•Both the Omega-3 Index and the n6:n3 ratio have been used to express PUFA status.•The n6:n3 ratio has become scientifically out-dated.•The Omega-3 Index, because if included EPA and DHA only, is a preferred metric. The well-known health effects of the long-chain, marine omega-3 (n-3) fatty acids (FAs) has led to a growing interest in the prognostic value that blood levels of these FAs might have vis-à-vis cardiovascular and neurocognitive diseases. The measurement and expression of n-3 FA levels is not straight-forward, however, and a wide variety of means of expression of n-3 FA status have been used in research and clinical medicine. This has led to considerable confusion as to what “optimal” n-3 FA status is. The n-6:n-3 ratio has enjoyed relatively widespread use, but this apparently simple metric has both theoretical and practical difficulties that have contributed to misunderstandings in this field. Just as the once-popular polyunsaturated:saturated FA ratio has largely disappeared from the nutritional and medical literature, it may be time to replace the n-6:n-3 ratio with a newer metric that focuses on the primary deficiency in Western diets – the lack of eicosapentaenoic and docosahexaenoic acids (EPA and DHA). The Omega-3 Index (red blood cell EPA+DHA) has much to recommend it in this regard.