The consumption of long chain omega-3 polyunsaturated acids (PUFA) is considered to protect against cardiovascular disease and promote longevity following a heart attack. Historically, research in this area was fuelled by compelling reports of the cardiovascular benefits of omega-3 PUFA in select populations and cultures. More recent studies, in wider populations, suggest discordant findings: differences that are difficult to reconcile as the mechanism of action of omega-3 PUFA are poorly understood. As such, the use of this 'natural treatment' for cardiovascular disease is increasingly controversial, and potentially one of unfulfilled promise. To what extent does ethnicity influence the impact that omega-3 PUFA have on cardiovascular disease and its associated complications? We were interested to review the benefits of omega-3 PUFA in the management of cardiovascular risk amongst diverse ethnic groups. Using a systematic review of literature relating to omega-3 PUFA and cardiovascular disease, we found ethnicity to be a factor that accounts for inconsistency between studies. Some of the effects of omega-3 PUFA are limited to cultures with a very high omega-3 intake, and in turn, ethnicity moderates the efficiency with which PUFA are derived from the diet. Moreover, omega-3 PUFA are an important health care intervention in the current climate of globalization, where supplementation is likely to give protection to cultural groups undergoing dietary transition. Future epidemiological research into the efficacy of omega-3 PUFA in cardiovascular disease should consider the influence of ethnicity.