An important concept for vascular remodeling, termed Glagov’s phenomenon, is that arteries remodel to maintain constant flow despite increases in atherosclerotic lesion mass. Although Glagov’s phenomenon was originally described only for the case of arterial remodeling in response to growth of atherosclerotic plaques, experimental and clinical observations indicate that blood flow properties influence remodeling after angioplasty, hypertension, and flow diversion as well as atherosclerotic plaque progression. This review attempts to define Glagov’s observation in terms of the physical parameters of blood in conduit arteries that must determine the remodeling response. Next we review experiments that have begun to identify specific molecules that influence vascular remodeling and therefore may serve as mediators for the phenomena. More comprehensive analyses of the specific molecular pathways in the vessels that determine constant flow may provide new therapeutic approaches to regulate vascular remodeling.