Cellular senescence is cell cycle stagnation caused by chronological aging or external stimulation. Atherosclerosis is regarded as the basic pathophysiological feature of coronary heart disease. Recent studies have found cellular senescence is an important mechanism for the development of atherosclerosis. Sirtuins, a family of cellular deacetylases, regulate the metabolism of cells and participate in the physiological functions of various cells. Previous studies have revealed the anti-ageing effect of Sirtuins, and suggested that Sirtuins are a group of longevity-associated proteins that can inhibit or reverse atherosclerosis by regulating cell aging. Herein, we reviewed the recent studies concerning Sirtuins, cellular aging and atherosclerosis, and discuss the feasibility of activating Sirtuins as a new strategy for combating atherosclerosis.