Protein kinases are phosphorylation enzymes that regulate signaling events in the cell and when impaired may be responsible for the pathophysiology seen in a number of disease states. Since these kinases only have activity when actively engaged in signaling events, most diseases are associated with dysregulation, dismutation, or impaired cellular regulation. The small GTP-binding protein, RhoA, and its downstream effector, Rho-kinase, have been implicated in the pathogenesis of a number of cardiovascular diseases. The activation of Rho-kinase is involved in the development of increased vascular tone, endothelial dysfunction, inflammation and restenosis, whereas the inhibition of Rho-kinase has been shown to have a beneficial effect in treatment of disease states involving dysregulation of Rho kinase. The X-ray analysis of the crystal structure of these protein complexes has revealed complex intermolecular interactions that are responsible for ligand binding and may allow for future design to optimize inhibitory protein kinase activity. The objective of this mini-review is to improve our current understanding of the role of RhoA/Rho-kinase pathway in the pathogenesis of cardiovascular diseases through the use of the Rho-kinase inhibitors, fasudil and Y-27632.