The most widely used mouse models for atherosclerosis are LDL receptor knockout (KO) mice and apolipoprotein E (apoE) KO mice fed standard chow diets or lipid-supplemented diets. Unfortunately, these do not usually exhibit myocardial infarction or other features of human cardiovascular disease such as occlusive coronary artery disease, cardiac dysfunction and/or reduced lifespan. Surgical models of myocardial infarction are successfully used for drug testing analyses during acute ischemia, but do not allow investigation of underlying mechanisms related to atherosclerotic coronary artery disease. Recently, experts in the pharmaceutical industry as well as some at the US Food and Drug Administration have identified inadequate animal models as being one of the major hurdles in drug discovery and development. There is an important need for additional well-characterized, genetically manipulable, small animal models that mimic many features of human coronary heart disease (CHD), which would provide investigators in academia and in the pharmaceutical industry with a better system to unravel the pathophysiology of atherosclerotic CHD and to evaluate preclinical drug candidates. Here we will review recently developed mouse models of occlusive CHD, focusing on mice lacking expression of the HDL receptor, SR-BI in the context of reduced expression of apoE.