Vascular inflammation is central to the pathogenesis of the atherosclerotic lesion. In the setting of hypercholesterolemia, vascular inflammation accelerates the accumulation of cholesterol within arterial smooth muscle cells, macrophages, and other immune cells. In disorders such as obesity, diabetes, and thrombosis, a myriad of interactions between sterol metabolites and inflammatory mediators exacerbate cholesterol deposition in the vessel wall, leading to the well-known consequences of stroke, transient ischemic attack, myocardial infarction, and peripheral vascular insufficiency. This review highlights emerging concepts in the regulation of cholesterol synthesis, the lipolytic enzymes involved in cholesterol utilization, and the therapies that successfully modulate vascular inflammation. In addition, developments relating to the role of inflammasomes in the management of cholesterol-mediated inflammation are discussed.