Autoregulation is a vital homeostatic mechanism that helps maintain constant delivery of oxygen to organs despite fluctuations in arteriolar pressure. Autoregulation of blood flow to elevations in pressure is largely mediated by the myogenic response of small arteries and arterioles which constrict in response to elevations in distending pressure. There is now general agreement that the myogenic response is an intrinsic property of vascular smooth muscle cells in the vessel wall that involves depolarization and calcium influx through L-type voltage-gated calcium channels (VGCC), calcium/ calmodulin-dependent phosphorylation of myosin light chain kinase and actin myosin-based contraction. Despite intensive investigation, however, the mechanotransduction events that initiate the myogenic response and the signaling pathways involved remain uncertain. This special issue on the Impact of Myogenic Tone in Health and Disease includes 9 papers that address current thought regarding the molecular mechanisms underlying myogenic control of vascular tone in the renal, cerebral and coronary circulations and the evidence that impairments in the myogenic response contribute to the development of vascular and end organ damage associated with hypertension, diabetes and aging.