The Metabolic Syndrome is a common metabolic disease associated with an increased risk for atherosclerotic cardiovascular disease and mortality. In contrast to "traditional" risk factors for atherosclerosis, such as low-density lipoprotein cholesterol, the Metabolic Syndrome represents a network of interacting risk factors stemming from the metabolic complexity of this disease. For this reason, dissection of the cellular and molecular pathways underlying atherosclerosis-susceptibility in the Metabolic Syndrome has been difficult. To facilitate this endeavor, several murine models have been recently developed. Despite their imperfect representation of the Metabolic Syndrome and atherosclerosis in humans, these models have provided important mechanistic insights and revealed novel molecular pathways. Furthermore, murine models are invaluable for the evaluation of therapeutic approaches and will no doubt facilitate the genetic dissection of atherosclerosis-susceptibility in the Metabolic Syndrome.