Atherosclerosis is an insidious and complex disease of large- and medium-sized arteries. The primum movens of the disease is characterized by co-localization of lipids, inflammatory cells, and fibrous elements within the intima of vessels. Starting as a "fatty streak," the disease evolves over decades into complex lesions that can progress toward a stable or a vulnerable plaque. During the past decade, we have become familiar with the features of the vulnerable plaque; however, the mechanisms that cause a stable plaque to change into a vulnerable lesion with its dramatic clinical outcome still remain largely unknown. There is good evidence from epidemiologic, experimental, and clinical studies that the renin-angiotensin system, via its active peptide angiotensin II, may contribute to atherosclerosis development and progression, not only by increasing blood pressure but also through multiple direct effects. Moreover, recent studies have shown a potential role for angiotensin II as a mediator of plaque vulnerability.