From the viewpoint of the prevention of cardiovascular disease (CVD) burden, there has been a continuous interest in the detrimental effects of the Western‐type high‐fat diet for more than half a century. More recently, this general view has been subject to change as epidemiological studies showed that replacing fat by carbohydrate may even be worse and that various polyunsaturated fatty acids (FA) have beneficial rather than detrimental effects on CVD outcome. At the same time advances in lipid biology have provided insight into the mechanisms by which the different lipid components of the Western diet affect the cardiovascular system. In fact, this still is a rapidly growing field of research and in recent years novel FA derivatives and FA receptors have been discovered. This includes fish‐oil derived FA‐derivatives with anti‐inflammatory properties, the so‐called resolvins, and various G‐protein coupled receptors that recognize FA as ligands. In the present review we will extensively discuss the role of FA and their metabolites on cardiac disease, with special emphasis on the role of the different saturated and polyunsaturated FA and their respective metabolites in cellular signal transduction and the possible implications for the development of cardiac hypertrophy and cardiac failure This article is protected by copyright. All rights reserved.