Traditionally, nutrients such as fatty acids have been viewed as substrates for the generation of high-energy molecules and as precursors for the biosynthesis of macromolecules. However, accumulating data from multiple lines of evidence suggest that dietary fatty acids are linked not only to health promotion but also to disease pathogenesis. Metabolism in humans is regulated by complex hormonal signals and substrate interactions. For many years, the clinical focus has centered on a wide metabolic picture after an overnight fast. Nonetheless, the postprandial state (i.e., "the period that comprises and follows a meal") is an important one, and silent disturbances in this period are involved in the genesis of numerous pathological conditions, including atherosclerosis. In this review article, we present an overview of the evidence demonstrating the relevance of oleic acid in olive oil on different nutrition-related issues. We also discuss the impact of oleic acid in olive oil and its clinical relevance to major risk factors for cardiovascular disease in the context of the postprandial state and with regard to other dietary fatty acids.