A growing body of evidence continues to emerge implicating the role of myeloperoxidase (MPO) and its oxidant products in the promotion of atherogenesis. A major mechanism by which MPO impacts the arterial wall is through its modification of net cellular cholesterol flux. MPO promotes lipid peroxidation and conversion of LDL to an atherogenic form, where it is taken up by macrophages, a critical step in foam cell formation. Emerging evidence suggests that HDL can also be modified by MPO derived oxidants, resulting in an impairment of cholesterol efflux. In addition, modified HDL appears to be a strong predictor of clinical risk. These features highlight MPO and its products as potential predictive markers and targets in atheroprotection.