Atherosclerosis patients develop life-threatening vascular syndromes including heart attach or stroke, largely due to disruption of silent, yet vulnerable plaques. Most recent series of studies on fatal myocardial infarction or sudden death due to coronary thrombosis have pointed to the underlying mechanism triggering rupture of plaques. Pathological investigations further illustrate the presence of significant amounts of lipids as well as high levels of inflammation in the ruptured or ruture-prone atherosclerotic plaques. Morphologic features of vulnerable plaques include a thinner cap, numerous activated T cells and macrophages, a pausity of smooth muscle cells, a lipid-rich necrotic core, eroded endothelium attached with microthrombi. In order to prevent plaque rupture and treat the vascular syndromes, it is important to detect or localize the plaques which are rupture-prone or vulnerable. Both invasive and non-invasive imaging technologies have been developed, and some of them are used in clinic. Primary and secondary preventation of atherosclerosis by eliminating the risk factors, hypercholesterolemia, hypertension, inflammation, and by changing life-styles have improve the arterial function and reduce the risk for plaque rupture. However, in spite of all the progress, scientists and clinicians still confront the challenge to promote regression of vulnerable plaques. Color graphics are presented at the end of the chapter.