Atherosclerosis is a disease in which deposits, called atherosclerotic plaques, build up in the arterial wall. Their presence can become critical when the plaques restrict blood flow and cause a stroke or a heart attack. Standard interventions to treat plaques and restore blood flow through an artery require the application of mechanical force to keep the plaque from obstructing the lumen. Because the cardiovascular system, and specifically blood vessels, has an essential mechanical function in maintaining health, understanding changes in mechanical behaviors in blood vessels caused by disease is critical. Therefore, studying blood vessel and plaque mechanical behaviors, and treating the tissues as materials, may provide essential information on predicting, treating, or preventing cardiovascular diseases. In this chapter, we discuss the current state of understanding of the mechanical behavior of atherosclerotic plaques. The mechanical behavior of a plaque will depend on its constituent materials and its geometry. We begin by discussing the nature of material properties, followed by a review of general arterial mechanics. Then we describe and discuss the studies that have investigated the mechanical responses of atherosclerotic plaques under different loading conditions. In summary, it is clear that our comprehension of the mechanical behavior of atherosclerotic plaque has made enormous advances in recent years. Unfortunately, there are still large gaps in our understanding of many aspects of cardiovascular disease: we still require better knowledge of plaque material properties and behaviors.