There has been increasing interest in the health benefits of supplemental and/or dietary omega-3 polyunsaturated fatty acids (PUFAs), particularly in their role in disease prevention. This interest escalated once their effects on cardiovascular health were observed from numerous observational studies in populations whose diet consisted mainly of fish. Research has since been undertaken on omega-3 PUFAs to investigate their health benefits in a vast array of medical conditions, including primary and secondary prevention. This article discusses the evidence and controversies concerning omega-3 PUFAs in various health conditions. In addition to the effects on cardiovascular health, omega-3 PUFAs have been shown to prevent the development of dementia, reduce systemic inflammatory diseases, prevent prostate cancer, and possibly have a role in the treatment of depression and bipolar disorder.