Atherosclerosis is the primary cause of coronary and cardiovascular diseases (CVD). Epidemiological studies have revealed several important environmental (especially nutritional) factors associated with atherosclerosis. However, progress in defining the cellular and molecular interactions involved has been hindered by the etiological complexity of the disease. Nevertheless, our understanding of CVD has improved significantly over the past decade owing to the availability of new randomized trial data. In particular, the failure of antioxidant and anti-inflammatory treatments to consistently reduce the rate of CVD complications suggests that theories of atherosclerosis may have considerably exaggerated the importance of oxidized lipoprotein and vascular inflammation. In that context, one new and basic question is whether the biology of essential dietary lipids may help us understand the role of the inflammatory process in CVD. Essential dietary lipids of the omega-6 and omega-3 families are the precursors of major mediators of inflammation such as eicosanoids that regulate the production of inflammatory cytokines and the expression of some major inflammation genes. On the other hand, non-essential lipids (omega-9 and saturated fatty acids) interfere with biological activities of essential lipids. Finally, essential omega-3 and omega-6 fatty acids have different, often antagonistic, effects on inflammation, and their effects can vary according to the type of cells and target organs involved, as well as their respective amounts in the diet. Because of the extreme complexity in the etiology of CVD, the best strategy may be to monitor the main features of dietary patterns, such as the Mediterranean diet, that are known to be associated with a low prevalence of both CVD and chronic inflammatory diseases.