This chapter examines whether a synergistic relationship exists between certain dietary fat constituents and whether the synergy alters cardiovascular risk parameters in a way that is more beneficial than that of each intervention alone. Results from numerous recent epidemiological studies have shown an inverse association between fish consumption and the risk of cardiovascular disease. Since fish oil supplementation alone has been shown repeatedly to decrease the risk of cardiovascular disease, researchers questioned whether there would be an additive or synergistic effect of fish oils when combined with other lipid constituents known for their antiatherogenic effect. Nonpharmacological interventions, such as diet and exercise, can help to control weight, blood pressure, and lipid abnormalities, thereby lowering the risk of adverse cardiovascular outcomes. Thus, combining such pharmacological therapies with certain dietary constituents, and favorably altering each lipid parameter, may be the optimal strategy for decreasing cardiovascular disease risk.