Growing evidences suggest that reactive oxidant species (ROS) are involved in the pathogenesis and progression of the atherosclerotic diseases. Markers assessing the oxidation of LDL and formation of eicosanoids, such as isoprostanes, were among the first that were analyzed. More recently, new biomarkers, such as endogenous secretory receptor for AGEs have been suggested to play an oxidative role in specific atherosclerotic settings, such as diabetes. Unfortunately, clinical trials included cross-sectional as well as retrospective and prospective studies which provide inconclusive results. Thus, clear evidence that oxidative biomarkers can improve risk stratification in addition to the common used atherosclerotic risk factors is still lacking. The analysis of oxidative stress focused on enzymatic systems generating ROS. The most studied enzymes were NADPH oxidase and myeloperoxidase (MPO). Experimental and clinical studies suggest that both enzymes may be implicated in promoting atherosclerotic disease. Novel laboratory methodologies have been, therefore, developed to study NADPH oxidase and MPO in patients with stable atherosclerosis as well in patients with acute coronary syndrome and cerebrovascular accident. This review will report on the more relevant studies in which the clinical application of the oxidative biomarkers was evaluated.