Restricting energy intake and increasing physical activity are advocated for reducing obesity, but many individuals have difficulty complying with these recommendations. Consumption of long-chain omega-3 polyunsaturated fatty acids (n-3 LCPUFA) offers multiple mechanisms to counteract obesity, including appetite suppression; circulatory improvements, which promote nutrient delivery to skeletal muscle and changes in gene expression, which shift metabolism toward increased fat oxidation; increased energy expenditure; and reduced fat deposition. n-3 LCPUFA may also alter gene expression in skeletal muscle to suppress catabolic pathways and upregulate anabolic pathways, resulting in greater lean tissue mass, metabolic rate, and maintenance of physical function. n-3 LCPUFA supplementation has been shown to counteract obesity in rodents, but evidence in humans is limited. Epidemiological associations between n-3 LCPUFA intakes and obesity are inconclusive. Several studies, on the other hand, indicate inverse relationships between biomarkers of n-3 LCPUFA status and obesity, although causality is uncertain. There have been few human intervention trials of omega-3 supplementation for obesity; some have indicated potential benefits, especially when combined with energy-restricted diets or exercise. More trials are needed to confirm these effects and identify mechanisms of action.