Acute aortic dissection (AAD) and associated ruptures are the leading causes of death in cardiovascular diseases (CVDs). Hypertension is a prime risk factor for AAD. However, the molecular mechanisms underlying AAD remain poorly understood. We previously reported that cyclic mechanical stretch (CMS) leads to the death of rat aortic smooth muscle cells (RASMCs). This review focuses on the mechanisms of CMS-induced vascular smooth muscle cell (VSMC) death. Moreover, we have also discussed the potential therapeutics for preventing AAD and aneurysm ruptures.