n-3 PUFA consumption improves vascular and cardiac hemodynamics, triglycerides, and possibly endothelial function, autonomic control, inflammation, thrombosis, and arrhythmia. Experimental studies confirm multiple relevant molecular effects, including on membrane structure and associated functions, ion channel properties, genetic regulation, eicosanoid synthesis, and production of novel inflammation-resolving mediators. Further experimental studies will be valuable to improve our understanding of which molecular mechanisms relate to specific effects of n-3 PUFA on risk factors and clinical endpoints. Not all trials of n-3 PUFA have demonstrated reductions in CVD, but several adequately powered clinical trials have documented significant benefits. When combined with the robust global evidence from observational studies, the documented effects on risk factors in short-term trials, and the experimental and mechanistic evidence, it is clear that n-3 PUFA are bioactive nutrients that play an important role in cardiovascular health, in particular for reducing risk of cardiac mortality. Additional appropriately designed and powered clinical trials are needed to assess effects of n-3 PUFA on other cardiovascular endpoints, including nonfatal coronary events, ischemic stroke, recurrent ventricular arrhythmias, AF, and heart failure. If the apparent nonlinear dose-response for CHD mortality extends to these other CVD outcomes, such trials might be most effective in individuals with little or no background fish intake. Additional studies should also address the potential of ALA and DPA to improve CVD risk factors and outcomes. As part of achieving a healthier overall dietary pattern that includes fruits, vegetables, whole grains, nuts, vegetable oils, and dairy (271), physicians should recommend fish consumption for their patients, and government and public health agencies should implement strategies to improve attainment of the recommended levels of fish and n-3 PUFA consumption to reduce population burdens of CHD mortality and sudden cardiac death.