The n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have demonstrated a beneficial effect on reducing morbidity and mortality of some highly prevalent chronic diseases. Therefore, there is considerable interest in establishing recommendations for EPA and DHA. The Institute of Medicine of The National Academies in 2002 established that 10% (~100 mg/day) of the acceptable macronutrient distribution range from α-linolenic acid (ALA) can be provided from EPA and DHA in order to avoid deficiencies and to support adequate neurodevelopment and growth. However, most of these data were obtained from epidemiological investigations rather than from clinical research. Additionally, this amount represents the average intake of these n-3 fatty acids in a healthy population but is not a dietary reference intake (DRI); hence, this amount has been qualified as low according to the scientific community. Considering the enormous health benefits based on several specific effects of n-3 LC-PUFAs, DRIs should be re-evaluated in light of the new evidence and the recommendations of numerous international federal agencies. At the present time, there is evidence of beneficial for prevention of coronary heart disease (CHD) and cardiac death at intakes of 250 to 500 mg/day of EPA + DHA as well for pregnant, lactating and childbearing woman whose daily consumption should be at least 200 mg of DHA. Meanwhile, evidence is inconclusive for preterm infants and other pathological entities such as cognitive decline and affective disorders.