Rho-family GTPases, including Cdc42, Rac1 and RhoA, regulate actin cytoskeleton and cell adhesion and play a central role in establishing cell polarisation. They also play an important role in cell growth and differentiation as well as transcriptional regulation. Migrating vertebrate cells in tissue culture display a characteristic polarization of the actin cytoskeleton. The dynamic organization of the actin cytoskeleton provides the force for cell motility and is regulated by small GTPases of the Rho family, in particular Rac1, RhoA and Cdc42. Cdc42 regulates cytoskeletal organization and membrane trafficking in physiological processes such as cell proliferation, motility and polarity. Aberrant activation of Cdc42 results in tumorigenesis, cardiovascular diseases, diabetes, and neurodegenerative diseases. The guanine nucleotide exchange factors (GEFs), which converse GDP-bound inactive form to the GTP-bound active form of Cdc42, are key components that transduce the upstream signals to Cdc42 and guide the interaction of active Cdc42 with a specific downstream effector. Zizimin1 (DOCK9) and ACG (DOCK11) are the specific GEFs for Cdc42.