RhoA is a member of the Rho protein family that has been identified as an essential regulator of vascular smooth muscle cell functions. Through the activation of its target Rho kinase, RhoA is the major regulator of the tonic component of vascular smooth muscle cell contraction and plays a critical role in the control of vascular smooth muscle differentiation, proliferation and migration. Aberrant activation of RhoA/Rho kinase signaling is involved in the pathogenesis of several vascular pathologies, including hypertension, coronary artery spasm, effort angina, atherosclerosis and restenosis. RhoA acts as molecular switches, that cycle between an inactive GDP-bound form and an active GTP-bound form. Guanine nucleotide exchange factors (GEFs) mediate the activation of RhoA by promoting the release of GDP in exchange for GTP. GTPase-activating proteins that stimulate intrinsic GTPase activity of RhoA, hydrolyze GTP to GDP then turn off activation. Rho GEFs are multidomain proteins that connect RhoA to numerous upstream receptors and signaling molecules. In particular, the subfamily of Rho GEFs that contains regulator of G-protein signaling (RGS) domain (Arhgef1, Arhgef11, Arhgegf12) mediates the activation of RhoA by G-protein-coupled receptors. Recent data and results, in particular on the regulation of Arhgef1 will be described to show that Rho GEF activity is regulated by phosphorylation by tyrosine kinases in vascular smooth muscle cells.