In many organs, blood flow is maintained at a relatively constant level although pressure changes substantially. This autoregulation of blood flow is achieved in several ways including the myogenic response (MR). MR is triggered by mechanical stretch of vascular smooth muscle. Activation of stretch activated channels (SACs) on vascular smooth muscle cells induces depolarization, Ca2+ influx and myogenic constriction. Nonselective cation channel, epithelial Na+ channel, chloride channel and potassium channel have been suggested as a molecular candidate of SAC. Additionally, activation of protein kinase C (PKC) and Rho-A kinase (ROK) contribute to MR without alteration of intracellular Ca2+. These complex interactions of Ca2+-dependent and Ca2+-sensitizing signals seem to be variable depending on the types of arteries as well as animal species. Finally, impaired MRs are related in various pathological conditions, such as hypertension, stroke and diabetes mellitus. Therefore, identification of MR signaling mechanism might be a target of treatment in vascular diseases.