There is growing consensus that systemic inflammation is at the heart of cardiovascular disease (CVD). Inflammation is a key feature of the immune system, functioning to defend tissue integrity and function. However, chronic stimulation of inflammatory mediators leads to lasting vascular reactivity, insulin resistance, hyperlipidemia, and, subsequently, chronic disease. Dietary practices to minimize inflammatory stimuli and CVD risk include regular intakes of fatty fish rich in the eicosapentaenoic and docosahexaenoic acids that compete with the more pervasive membrane fatty acid, arachidonic acid, disrupting the metabolic cascades that stimulate inflammation. Another effective dietary strategy is to consume less arachidonic acid by reducing beef, poultry, fish, and eggs from the diet (e.g., adopting a vegetarian-like diet). Since oxidative stress plays a prominent role in immune system activation, regular ingestion of ample amounts of fruits and vegetables (8+ servings/d) rich in antioxidant compounds, the polyphenols, carotenoids, and vitamin C (e.g., citrus, tomatoes, berries, carrots, and greens), lowers inflammatory mediators and risk for chronic disease. Whole grains, legumes, and nuts have also been demonstrated in clinical trials to effectively reduce inflammatory mediators and risk for CVD. Hence, as proclaimed in antiquity, 'let food be thy medicine and medicine be thy food'.