Atherosclerosis and its sequelae are key contributors to overall human morbidity and mortality worldwide. Substantial effort has been made toward the understanding of disease mechanisms and particularly treatment options. Drugs for primary and secondary prevention of atherosclerosis and in particular its complications, e.g., myocardial infarction, are widely used therapeutics. However, those drugs typically act nonspecifically, thus affecting not only target cells and atherosclerotic lesions but also causing unwanted side effects. One of the most promising recent developments are drugs that exclusively act at the site where they are needed and thereby minimize deleterious side effects. This review focuses on new approaches for targeted drug delivery, emphasizing single-chain antibody constructs, liposomal formulations, and microRNAs/gene delivery to sites of atherosclerosis and thrombosis.