Omega-3 fatty acids (FAs), which include eicosapentaenoic acid (EPA) and docosahexaenoic acid, are found in fish oils and have long been investigated as components of therapy for various disease states. Population studies initially revealed the cardioprotective and anti-inflammatory effects of omega-3 FAs and EPA, with subsequent clinical studies supporting the therapeutic role of omega-3 FAs in cardiovascular and chronic inflammatory conditions. Prospective randomized placebo-controlled trials have also demonstrated the utility of omega-3 FA supplementation in malignancy and cancer cachexia. In recent years, in vitro and animal studies have elucidated some of the mechanistic explanations underlying the wide range of biological effects produced by omega-3 FAs and EPA, including their antiproliferative and anticachectic actions in malignancy. In this review, the authors discuss the recent progress made with omega-3 FAs, focusing on the advances in mechanistic understanding and the results of clinical trials.