Cardiovascular disease is the major cause of death in most developed nations and the social and economic burden of this disease is quite high. Atherosclerosis is a major underlying basis for most cardiovascular diseases including myocardial infarction and stroke. Genetically modified mouse models, particularly mice deficient in apoprotein E or the LDL receptor, have been widely used in preclinical atherosclerosis studies to gain insight into the mechanisms underlying this pathology. This chapter reviews several mouse models of atherosclerosis progression and regression as well as the role of immune cells in disease progression and the genetics of murine atherogenesis.