Rho GTPases such as Rac1, Rac2, Cdc42, RhoA, RhoH, and guanine nucleotide exchange factor Vav regulate hematopoietic stem and progenitor functions. Cdc42, Rac1, and RhoA control the self-renewal, and Cdc42 is required for cell cycle entry of quiescent HSCs. Rac1 and Cdc42 control proliferation, whereas Rac2 and Cdc42 regulate survival HSC/Ps. Rac1 and Cdc42 regulate HSC homing to the bone marrow microenvironment. Rac1, Rac2, and CDC42 control the retention of HSC in the bone marrow microenvironment. Vav1, a hematopoietic specific guanine nucleotide exchange factor, regulates localization of HSCs near nestin+ mesenchymal stem cells. The aged HSCs shows elevated level of Cdc42, and increased Cdc42 level is correlated with loss of the polarity and self-renewal activity. HSC/P, hematopoietic stem cells and progenitors.