Dendritic spines are the postsynaptic sites for the majority of excitatory synapses in the mammalian forebrain. While many spines display great stability, others change shape in a matter of seconds to minutes. These rapid alterations in dendritic spine number and size require tight control of the actin cytoskeleton, the main structural component of dendritic spines. The ability of neurons to alter spine number and size is essential for the expression of neuronal plasticity. Within spines, guanine nucleotide exchange factors (GEFs) act as critical regulators of the actin cytoskeleton by controlling the activity of Rho-GTPases. In this review we focus on the Rho-GEFs expressed in the nucleus accumbens and localized to the postsynaptic density, and thus positioned to effect rapid alterations in the structure of dendritic spines. We review literature that ties these GEFs to different receptor systems and intracellular signaling cascades and discuss the effects these interactions are likely to have on synaptic plasticity.