GTPases of the Ras superfamily act as molecular switches to control a wide range of essential biochemical pathways in all eukaryotic cells. Among the 60 or so that have been identified so far in mammalian cells, the Ras and the Rho families are of special interest since they couple intracellular signal transduction pathways to changes in the external environment. Like all GTPases, they exist in an inactive (GDP-bound) and an active (GTP-bound) conformation. Guanine nucleotide exchange factors (GEFs) catalyze the release of GDP, allowing GTP to bind (its intracellular concentration is higher than that of GDP). In their active, GTP-bound state, Ras and Rho GTPases interact with target proteins to promote a cellular response. Finally, an intrinsic GTPase activity, catalyzed further by GTPase activating proteins (GAPs), completes the cycle and the GTPase returns to its inactive, GDP-bound state. Figure 1 shows some of the upstream GEFs, downstream targets, and GAPs for two examples, Ras itself, and Rac, a member of the Rho family.