The family of polyunsaturated fatty acids (PUFAs), which can be found in most lipid classes, includes n-3 PUFAs essential for mammals and whose deficiency is associated with multiple diseases. Because of their multiple physiological actions, n-3 PUFAs play a crucial role in normal human metabolism as well as maintenance of a healthy status, with clinical effects that are not limited to the cardiovascular system but also include maternal and offspring health, growth and development, immune system disorders, cancer, cognitive function and psychological status. Multiple health organisations and scientific societies recommend increasing food-derived n-3 PUFA intake and also suggest that patients with documented coronary heart disease receive a minimum of 1000 mg/day of eicosapentaenoic acid and docosahexaenoic acid. The preventive and therapeutic effects of n-3 PUFAs appear to be largely dependent on the dosages employed and the characteristics of selected patients. So, in the era of personalised medicine, the time has come to move from generic advice to increase n-3 PUFA intake to a more evidence-based approach characterised by tailored indications to n-3 PUFA dietary or supplement consumption. This approach will require evaluation on a case-to-case basis the potential usefulness of n-3 PUFAs, taking into consideration their 'pleiotropic effects', the optimal dose for any given indication in relation to international guidelines, potential interactions with background therapy, possible side effects, differences in genetics and dietary response to supplementation, and the cost: benefit ratio, which is likely to vary as a function of differences in the range of fish intake in the diet. (C) 2013 Elsevier Ireland Ltd. All rights reserved.