Rho GTPases regulate many important processes in all eukaryotic cells, including the organization of the actin cytoskeleton, gene transcription, cell cycle progression, and membrane trafficking. Their activity is regulated by signals originating from different classes of surface receptors including G-protein-coupled receptors, tyrosine kinase receptors, cytokine receptors, and adhesion receptors. Recent work has identified multiple mechanisms by which receptors can signal to Rho GTPases and this will be the major focus of this review. In addition, there is growing evidence for cross-talk within the Rho GTPase family as well as between the Rho and Ras GTPase families. These signaling networks are thought to provide the cooperative and coordinated interactions that are crucial for regulating complex biological processes such as cell migration.