Approximately 2% of genes predicted by the sequenced human genome encode small GTPases and their regulators, highlighting the biological significance of regulated GTPase activity. Among the key GTPase regulators are the GTPase activating proteins (GAPs), which function to down-modulate active GTPases. Of the numerous identified GAPs, several have been implicated in signal transduction downstream of growth factors. In particular, GAPs for the Ras and Rho GTPases, which mediate a variety of receptor-transduced signals, appear to play an essential role in growth factor dependent GTPase regulation. Experimental studies of several of the GAPs have begun to elucidate mechanisms by which GAP activity is influenced by growth factor signaling, including direct phosphorylation, sub-cellular redistribution and protein degradation. Here, some of these mechanisms of GAP regulation in the context of signaling responses to growth factors are reviewed.