Plasma sphingomyelin concentration is correlated with the development of atherosclerosis. It has been found to exist in significantly higher concentrations in aortic plaque. This appears to have clinical relevance as well as it has been shown to be an independent predictor of coronary artery disease. Ceramide, the backbone of sphingolipids, is the key component which affects atherosclerotic changes through its important second-messenger role. This paper sheds light on some of the current literature supporting the significance of ceramide with respect to its interactions with lipids, inflammatory cytokines, homocysteine and matrix metalloproteinases. Furthermore, the potential therapeutic implications of modulating ceramide concentrations are also discussed.