The advent of nanotechnology in the medical arena has led to unique ways of biomaterials engineering and device modifications, disease detection and treatment. To this end, the two principal nanomedicine focus areas are cancer and cardiovascular pathologies. The current chapter is aimed at presenting a comprehensive review of nanotechnology-based strategies in cardiovascular diseases, with emphasis on targeted delivery of therapeutic payloads selectively at the disease site. The rationale for such strategies stem from the need of resolving the issues of (1) rapid drug clearance, (2) plasma-induced drug deactivation, (3) suboptimal drug availability at the disease site, and (4) indiscriminate biodistribution of the drugs leading to harmful systemic side effects, all of which arise when drugs are administered directly in systemic circulation. The most significant application of nanotechnology in resolving these issues is by packaging the drugs within plasma-stable nanovehicles that can preferentially accumulate at the vascular disease site via passive uptake or bind actively to the site via antigen-specific ligands decorated on the vehicle surface. During past three decades, significant advancements in understanding vascular disease-associated genomics and proteomics, cellular and molecular mechanisms as well as nanoscale and microscale strategies of biomaterials engineering have led to several exciting nanomedicine approaches in vascular disease treatment. The chapter will describe these approaches in terms of materials engineering, payload release mechanisms, biochemical and biophysical design parameters of the delivery platforms, and integration of multiple design parameters and functionalities on single vehicle platform, along with discussing the promises and limitations of such vascular nanomedicine approaches.