Strategies that enhance the number of endothelial cells (ECs) in the vessel wall following injury may limit complications such as thrombosis, vasospasm, and neointimal formation through reconstitution of a luminal barrier and cellular secretion of paracrine factors. Proof of principle has been demonstrated by studies in which mature ECs, culture expanded from harvested vascular tissue, were seeded in the arterial wall following balloon injury. The recent identification of circulating cells capable of developing an endothelial phenotype, including progenitor cells, has raised the possibility of using blood-derived cells as therapeutic agents. This article reviews data suggesting that such cells confer vascular protective effects after injury, raising the potential for novel, autologous approaches to the treatment of vascular disease.