Most excitatory synapses reside on small protrusions located on the dendritic shaft of neurons called dendritic spines. Neuronal activity regulates the number and structure of spines in both developing and mature brains. Such morphological changes are mediated by the modification of the actin cytoskeleton, the major structural component of spines. Because the number and size of spines is tightly correlated with the strength of synaptic transmission, the activity-dependent structural remodeling of a spine plays an important role in the modulation of synaptic transmission. The regulation of spine morphogenesis utilizes multiple intracellular signaling pathways that alter the dynamics of actin remodeling. Here, we will review recent studies examining the signaling pathways underlying activity-dependent actin remodeling at excitatory postsynaptic neurons. (c) 2012 Wiley Periodicals, Inc