Atherosclerosis and its resultant cardiovascular events represent a state of heightened oxidative stress that is commonly thought to contribute to atherogenesis. The aim of this review is to summarize the data linking oxidative events to the pathogenesis of atherosclerosis. Despite abundant data supporting the presence of lipid and protein oxidation in the vascular wall, the poor performance of antioxidant strategies in limiting either atherosclerosis or cardiovascular events from atherosclerosis remain a fundamental problem for implicating oxidative stress as pathophysiologically important. Direct evidence that oxidative stress in general, and the oxidative modification of low-density lipoprotein in particular, is both necessary and sufficient for atherosclerosis has been difficult to find. There are many potential reasons for this difficulty, not the least of which is our lack of sufficient knowledge delineating the precise molecular events that beget oxidative stress in the vessel wall, and the precise mediators involved. Further investigation elucidating these oxidative events are required to provide us with the tools to limit oxidative stress at its source and ameliorate all of its secondary phenomena. Only then will we know what components of atherosclerosis are directly due to oxidative stress.