Modest consumption of fish (eg, 1-2 servings/wk), especially species higher in the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduces risk of coronary death by 36% (95% confidence interval, 20%-50%; P<.001) and total mortality by 17% (95% confidence interval, 0%-32%; P = .046) and may favorably affect other clinical outcomes. Intake of 250 mg/d of EPA and DHA appears sufficient for primary prevention. DHA appears beneficial for, and low-level methylmercury may adversely affect, early neurodevelopment. Women of childbearing age and nursing mothers should consume 2 seafood servings/wk, limiting intake of selected species. Health effects of low-level methylmercury in adults are not clearly established; methylmercury may modestly decrease the cardiovascular benefits of fish intake. A variety of seafood should be consumed; individuals with very high consumption (> or =5 servings/wk) should limit intake of species highest in mercury levels. Levels of dioxins and polychlorinated biphenyls in fish are low, and potential carcinogenic and other effects are outweighed by potential benefits of fish intake and should have little impact on choices or consumption of seafood (women of childbearing age should consult regional advisories for locally caught freshwater fish).