Nutrition is central to optimizing training adaptation and performance. Dietary fish oil provides long chain omega-3 polyunsaturated fatty acids (LC n–3 PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that are essential for biological function beyond providing metabolic energy. Emerging evidence demonstrates fish oil, without compromising carbohydrate or protein, can support the physiological stress of exhaustive exercise via direct modulation of systems physiology. Intake of DHA-rich fish oil elevates the erythrocyte omega-3 index, reflective of heart and skeletal muscle incorporation, and modulates oxygen usage during exercise without compromise to maximal aerobic power. Alternatively, the emerging role of circulating EPA has primarily focused upon immune and inflammatory support, including muscle damage, where preliminary evidence suggests attenuation of inflammatory response in less trained individuals. Future studies will need to further consider the biological difference that DHA can offer in these fields. Despite physiological benefits, provision of dietary fish oil has not yet been demonstrated to have performance enhancing effects in well-trained or elite athletes. Nonetheless, there are specific exercise conditions that are discussed in this chapter that warrant further investigations. Notwithstanding, these studies must occur with the highest standards of biological plausibility including monitoring of tissue incorporation and implementing study design in agreement with the most recent recommendations for demonstrating interaction of nutrition and performance.