Cardiovascular diseases (CVDs) are the most abundant causative factors of mortality and morbidity in the world specifically in the developing countries. Many studies on humans and animals prove that inflammation plays a key role in the initiation and propagation of the process of atherosclerosis. Interleukin-27 (IL-27) is a new IL-12/IL-6 family member which is a heterodimeric multifunctional pro- and anti-inflammatory cytokine. IL-27 one of the important cytokines distinguished in atherosclerotic plaques. In this review, we demonstrate the coronary artery disease and its pathogenesis, the role of inflammation in the initiation and progression of atherosclerosis, IL-27, IL-27 receptors and signaling pathway, pro and anti-inflammatory characters of IL-27 and finally the effect of IL-27 as an inflammatory mediator in the process of atherogenesis.