Advances made over the past few years have made us appreciate the critical roles of Rho-associated kinase (Rho-kinase/ROCK) in a bewildering variety of cellular and biological responses. Rho-kinase represents a downstream target for the low–molecular-weight G-protein, Rho, and is believed to transmit signals to cytoskeletal and regulatory proteins. In recent years, enormous progress has been made in understanding the role of this signaling pathway in regulating cellular movements, cell growth, and cell–cell interactions. Rho-kinase has been implicated in many cellular processes, such as stress fiber and focal adhesion formation, smooth muscle contraction, neurite retraction, and cell migration.1,2 In addition to Ca2+-dependent increases in myosin light chain (MLC) phosphorylation for vascular contraction to occur, the concept of a Ca2+-sensitizing mechanism for the promotion of the phosphorylated state of MLC has become evident.3 Extensive studies demonstrate that the sustained contractile force in vascular smooth muscle preparations generated on agonist stimulation does not parallel intracellular Ca2+ levels. On exposure to an agonist, Ca2+ concentration in the cytosol peaks and then quickly drops to near-resting levels despite the maintenance of contractile force. Further, tonic force generation in many vascular preparations persists in Ca2+-free media, further implicating an increase in Ca2+ sensitivity of the contractile apparatus, or the activation of a Ca2+-independent mechanism.4,5 This phenomenon has been termed agonist-induced force enhancement, or Ca2+ sensitization, and several mechanisms have been proposed.3,6 Although the signaling pathway(s) for Ca2+ sensitization have not been fully elucidated, the most proposed mechanism converges on an inhibition of MLC phosphatase activity through the Rho/Rho-kinase–linked pathway.3 In this issue of Circulation Research , Bailey et al7 provide compelling evidence that, under cooling conditions, the Rho/Rho-kinase signaling pathway is activated to mediate cold-induced constriction in …