Atherosclerosis is a disease of large- and medium-sized arteries. Complications from atherosclerosis remain a serious cause of morbidity and mortality in industrialized countries. The disease begins very early in life and effects most people in the West. However, because the progression of the disease is slow, symptoms usually do not occur until after the fifth decade of life. Because atherosclerosis is a ubiquitous occurrence throughout the world, as life expectancy is prolonged most populations will see increasing numbers of deaths from complications of atherosclerosis unless there are dramatic advances in treatment. Because it begins so early in life, current treatment is aimed at slowing or reversing the progression of the disease rather than eliminating the initiating steps. Changes in diet and exercise, cholesterol-lowering drugs, and improvements in surgical treatments have made significant inroads into prolonging life, but much work is still required. To proceed further, a better understanding is needed of the underlying causes of disease progression. In this regard, evidence is mounting that the foam cells of the lesion (a critical cell in atherosclerosis progression) exhibit characteristics of an acquired lysosomal storage disorder. In this review the evidence for this conclusion is reviewed and the ramifications of this conclusion are explored with regard to the understanding of disease progression mechanisms, possible improvements in treatment, and their role in increasing life expectancy.