Despite myriad advances, cardiovascular-related diseases continue to remain our greatest health problem. In more than half of patients with atherosclerotic disease, their first presentation to medical attention becomes their last. Patients often survive their first cardiac event through acute revascularization and placement of drug-eluting stents (DES), but only select coronary lesions are amenable to DES placement, resulting in the use of bare metal or no stent, both of which lack the benefit of antirestenotic therapy. In other patients, transient ischemic attacks (TIAs) and stroke constitute the initial presentation of disease. In these patients, the diagnostic and therapeutic options are woefully inadequate. Nanomedicine offers options to each of these challenges. Antiangiogenic paramagnetic nanoparticles may be used to serially assess the severity of atherosclerotic disease in asymptomatic, high-risk patients by detecting the development of plaque neovasculature, which reflects the underlying lesion activity and vulnerability to rupture. The nanoparticles can locally deliver antiangiogenic therapy, which may acutely retard plaque progression, allowing aggressive statin therapy to become effective. Moreover, these agents may be useful as a quantitative marker to guide atherosclerotic management in an asymptomatic patient. In those cases proceeding to the catheterization laboratory for revascularization, nanoparticles incorporating antirestenotic drugs can be delivered directly into the wall of lesions not amenable to DES placement. Targeted nanoparticles could help ensure that antirestenotic drugs are available for all lesions. Moreover, displacement of antiproliferative agents from the intimal surface into the vascular wall is likely to improve reheating of the endothelium, improving postprocedural management of these patients.