Glutamatergic axons in the mammalian forebrain terminate predominantly onto dendritic spines. Long-term changes in the efficacy of these excitatory synapses are tightly coupled to changes in spine morphology. The reorganization of the actin cytoskeleton underlying this spine "morphing" involves numerous proteins that provide the machinery needed for adaptive cytoskeletal remodeling. Here, we review recent literature addressing the chemical architecture of the spine, focusing mainly on actin-binding proteins (ABPs). Accumulating evidence suggests that ABPs are organized into functionally distinct microdomains within the spine cytoplasm. This functional compartmentalization provides a structural basis for regulation of the spinoskeleton, offering a novel window into mechanisms underlying synaptic plasticity.