Accelerated atherosclerosis is both a cause and a consequence of chronic renal failure. Vascular smooth muscle cells (VSMCs) are an important component of atherosclerotic plaques, responsible for promoting plaque stability in advanced lesions. In contrast, VSMC apoptosis has been implicated in a number of deleterious consequences of atherosclerosis, including plaque rupture, vessel remodelling, co- agulation, inflammation and calcification. Although VSMC apoptosis occurs in association with these processes, its precise contribution to these diseases is unknown, given that apoptosis frequently accompanies vessel injury or alterations to flow. Using transgenic mice with selective induction of VSMC apoptosis, a recent study has precisely determined the direct consequences of VSMC apoptosis in both normal vessels and atherosclerotic plaques. Surprisingly, normal arteries can withstand huge cell losses with little change in active or passive properties. Normal vessels demonstrate highly efficient clearance of apoptotic bodies, even in the absence of professional phagocytes. In contrast, VSMC apoptosis alone is sufficient to induce multiple features of vulnerability to rupture in plaques. This study identifies VSMC apoptosis as a critical process determining plaque stability and thus the most important consequence of atherosclerosis, plaque rupture.