Endothelial repair is essential in preventing or limiting fibroinflammatory atheroma formation and growth as well as limiting the complications of erosion, fissure formation, and rupture from occurring. The integrity of the endothelium depends to a large extent on the integrity of the cytoskeleton in the cell. It is likely that the repair of the integrity of the endothelium will depend, at least in part, on the ability of the endothelial cell (EC) to regulate patterns of interaction between cytoskeletal networks, especially microfilaments (MFs) and microtubules (MTs). A well-integrated cytoskeleton is believed to be required for efficient cell spreading, cell migration, and cell proliferation—the essential processes for endothelial repair. Thus, the endothelial cytoskeleton is indeed a potential treatment target for the prevention and treatment of atherosclerotic disease at the endothelial level.