Cardiovascular disease is the leading cause of death in the United States. According to numbers compiled by the American Heart Association, nearly one of every two Americans dies of cardiovascular disease. For example, in 1987, 976,706 (46%) of the estimated 2,127,000 deaths recorded in the United States were attributable to diseases of the heart and blood vessels [1]. Most of these deaths can be attributed to atherosclerosis and its ensuing complications. The pathogenesis of atherosclerosis is not completely understood. Nevertheless, the purpose of this review is to provide an overview of how an atherosclerotic lesion might develop on the basis of our current understanding. This overview will focus on one hypothesis of atherosclerosis development, the modified response-to-injury hypothesis. Several additional hypotheses will be described briefly. These descriptions can serve as a framework on which researchers can build a more complete understanding of the processes involved in this complicated, multifactorial disease.