Though multiple pharmacological treatments for cardiovascular disease exist, it has been shown that certain dietary interventions or supplements may provide similar, yet more cost-effective, benefits. Certain dietary fat constituents, occurring either as natural components of food or as nutritional supplements, have been shown to favorably alter indicators of cardiovascular disease risk when administered to various population groups. Examples of such lipid compounds include fish oils, medium chain triglycerides (MCT), and plant sterols. Though the independent effects of these compounds have been thoroughly studied, their cardioprotective effects when administered in combination have yet to be fully defined. Therefore, the aim of this chapter is to examine whether a synergistic relationship exists between certain dietary fat constituents and whether this synergy alters cardiovascular risk parameters in a way that is more beneficial than that of each intervention alone. Additionally, the potential synergistic relationships between certain dietary lipids and drug therapies used to treat cardiovascular disease are also elucidated. Furthermore, the safety profiles of these foods when administered alone, or in combination, are explored.