Nearly all excitatory input in the hippocampus impinges on dendritic spines which serve as multifunctional compartments that can, at the very least, selectively isolate and amplify incoming signals. Their importance to normal brain function is highlighted by the severe mental impairment observed in most individuals having poorly developed spines (Purpura, Science 1974;186:1126-1128). Distinct groups of membrane proteins, cytoskeletal elements, scaffolding proteins, and second messenger-related proteins are concentrated particularly in dendritic spines, but their ability to generate, maintain, and coordinately regulate spine structure or function is poorly understood. Here we review the unique molecular composition of dendritic spines along with the factors known to influence dendritic spine development in order to construct a model of dendritic spine development in relation to synaptogenesis.