Inflammation and oxidative stress play central roles in the pathogenesis of atherosclerosis and outcomes such as myocardial infarction and stroke. The enzyme myeloperoxidase (MPO) is secreted by activated leukocytes in atherosclerotic plaques and generates several pro-oxidative species that participate in biological activities that promote plaque destabilization and rupture; the catastrophic event that defines which plaques are benign and which are life-threatening. Serum MPO levels are also highly predictive of downstream cardiovascular events and patient outcome. Recently, several molecular imaging probes sensitive to the presence of MPO activity have been developed. Here we review the design and application of probes developed for MRI, single photon emission CT, and fluorescence and bioluminescence imaging. Continued development of these probes may one day allow detection of plaques prior to plaque rupture, yielding significant diagnostic and prognostic improvements and ultimately allowing proper staging and treatment of high-risk patients.