Mouse models have become the most common model for defining mechanisms of atherosclerotic disease. Many genetic manipulations have enabled the development of atherosclerosis in mice due to either endogenous or diet-induced hypercholesterolemia. This availability of lesion-susceptible mice has facilitated many studies using pharmacological and genetic approaches. Unfortunately, this expansive literature on mouse atherosclerosis has generated many contradictions on the role of specific pathways. A contributor to these inconsistencies may be the multiple modes in which atherosclerosis is evaluated. Also, for each specific technique, there are no consistent standards applied to the measurements. This chapter will discuss the imaging, biochemical, and compositional modes of evaluating atherosclerosis with suggestions for standard execution of these techniques.