For many growing axons, interaction with an extracelluar Semaphorin signal leads to growth cone collapse and axon repulsion. Semaphorin receptors composed of Neuropilins and Plexins transduce extracellular cues into changes in the growth cone actin cytoskeleton. The data implicating Rho family G proteins in Semaphorin signaling and in other axon guidance events are considered here. Recent work makes it clear that Rac1 is required for this process. In particular, there is intriguing new evidence that the Plexin receptors communicate directly with members of the Rho family GTPases, although uncertainties remain concerning how Plexins alter Rac1 function. The CRMP (collapsin response mediator protein) family is also required for Plexin-based Semaphorin signaling, and new data demonstrate direct links to Rho and Rac1-based signaling.