▪ Abstract Microtubules are dynamic polymers required for many aspects of eukaryotic cell function. The interphase microtubule network is essential for intracellular transport, organization, and cell polarization, whereas the mitotic spindle is required for chromosome segregation and cell division. Studies in different areas such as cell migration, mitosis, and asymmetric cell division have shown that Ran, Rho, and heterotrimeric G proteins regulate many aspects of microtubule functions. This review surveys how G protein–signaling coordinates microtubule polymerization and organization with specific cellular activities.