With increasing understanding of the cellular and molecular processes involved in atherosclerosis, new insights have been gained into the contributions of various pathways to atherosclerosis development. Myeloperoxidase, a leukocyte enzyme that is part of the innate immune response, is present, active, and believed to be functionally involved in plaque development and complications. The use of myeloperoxidase levels in risk stratification is an example of a mechanistically linked biomarker. This review focuses on recent literature and background relevant to examining the role and potential clinical use of myeloperoxidase in cardiovascular disease.