Atherosclerosis is responsible for more than half of all deaths in western countries. Numerous studies have reported that exuberant accumulation of smooth muscle cells (SMCs) plays a principal role in the pathogenesis of occlusive vascular diseases. It has been assumed that SMCs derived from the adjacent medial layer migrate towards the atherosclerotic lesion, proliferate and synthesize extracellular matrix, thus contributing to atheroma growth. Although much effort has been devoted to targeting the migration and proliferation of medial SMCs, no effective therapy to prevent occlusive vascular remodeling has been established. By taking advantage of genetically-modified mice, we recently reported that bone marrow cells substantially contribute to the pathogenesis of vascular diseases. It was suggested that bone marrow cells may have the potential to give rise to vascular progenitor cells that home in the damaged vessels and differentiate into smooth muscle cells or endothelial cells, thereby contributing to vascular repair, remodeling, and lesion formation. This article summarizes what we learned from genetically-modified animals regarding the origins and the fates of vascular cells that contribute to lesion formation.