Administration of drugs and other therapeutic agents has been the central strategy of contemporary medicine for cardiovascular disease. The use of a drug delivery system (DDS) is always demanded to enhance the efficacy and safety of therapeutic agents, and improve the signal-to-noise ratio of imaging agents. Nano-scale materials modify in vivo drug kinetics, depending on (patho)physiological mechanisms such as vascular permeability and incorporation by the mononuclear phagocyte system, which constitute 'passive-targeting' properties of nano-DDS. By contrast, an 'active-targeting' strategy employs a specific targeting structure on nano-DDS, which binds to the target molecule that is specific for a certain disease process, such as tumor specific antigens and the induction of adhesion molecules. In this review, we summarize recent studies that applied nano-DDS for the diagnosis and treatment of cardiovascular disease, especially focusing on atherosclerosis and myocardial ischemia-reperfusion (IR) injury. Pathophysiological changes in atherosclerosis and myocardial IR injury are successfully targeted by nano-DDS and preclinical studies in animals showed positive effects of nano-DDS enhancing efficacy and reducing adverse effects. The development of nano-DDS in clinical medicine is keenly being awaited.