The role of cytokines in the pathogenesis of cardiovascular disease is increasingly evident since the identification of immune/inflammatory mechanisms in atherosclerosis and heart failure. In this review, we describe how innate and adaptive immune cascades trigger the release of cytokines and chemokines, resulting in the initiation and progression of atherosclerosis. We discuss how cytokines have direct and indirect effects on myocardial function. These include myocardial depressant effects of nitric oxide (NO) synthase-generated NO, as well as the biochemical effects of cytokine-stimulated arachidonic acid metabolites on cardiomyocytes. Cytokine influences on myocardial function are time-, concentration-, and subtype-specific. We provide a comprehensive review of these cytokine-mediated immune and inflammatory cascades implicated in the most common forms of cardiovascular disease.