Inflammation links obesity with the development of insulin resistance. Macrophages and phagocytic immune cells communicate with metabolic tissues to direct an inflammatory response caused by overnutrition and expanding adipose tissue. Marine-derived omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), modulate inflammatory signalling events, providing various anti-inflammatory and cardioprotective benefits. Moreover, EPA and DHA may improve insulin sensitivity by generating proresolving lipid mediators and promoting alternatively activated macrophages. This review will assess the role of EPA and DHA in ameliorating obesity-induced inflammation, evaluating clinical evidence and mechanisms of action. The pathophysiology of insulin resistance resulting from obesity-induced inflammation will be discussed, highlighting the relationship between metabolism and immunity, and in particular, how EPA and DHA work with both systems to modulate immunometabolic complications and chronic disease. Copyright © 2013 John Wiley & Sons, Ltd.