Atherosclerosis is a complicated pathophysiological process characterized by the accumulation of atheromatous plaque in the arterial wall and subsequent narrowing of the arteries, and it is one of the major causes of the high mortality and disability in cardiovascular disease. The initiation and progression of atherosclerosis is a chronic degenerative process with complicated mechanisms involving multiple cells and molecules. Oxidative stress, a series of adaptive responses caused by the imbalance between reactive oxygen species and antioxidant system, is considered as one of the crucial mechanisms in the development of atherosclerosis. This review presents the relationship between oxidative stress and atherosclerosis from the perspective of the different sources of reactive oxygen species in the organism, summarizes the effects of oxidative stress on different cells, biomolecules and biological processes in atherosclerosis, and briefly describes the clinical research and applications of antioxidant agents in the treatment of atherosclerosis.