The beneficial effects of consuming omega-3 polyunsaturated fatty acids (n-3 PUFAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cardiovascular health have been studied extensively. To date, there is no dietary reference intake (DRI) for EPA and DHA, although many international authorities and expert groups have issued dietary recommendations for them. Given the substantial new evidence published since the last Institute of Medicine (IOM) report on energy and macronutrients, released in 2002, there is a pressing need to establish a DRI for EPA and DHA. In order to set a DRI, however, more information is needed to define the intakes of EPA and DHA required to reduce the burden of chronic disease. Information about potential gender- or race-based differences in requirements is also needed. Given the many health benefits of EPA and DHA that have been described since the 2002 IOM report, there is now a strong justification for establishing a DRI for these fatty acids.