Dendritic spines mediate most excitatory synapses in the CNS and are therefore likely to be of major importance for neural processing. We review the structural aspects of dendritic spines, with particular emphasis on recent advances in the characterization of their molecular components. Spine morphology is very diverse and spine size is correlated with the strength of the synaptic transmission. In addition, the spine neck biochemically isolates individual synapses. Therefore, spine morphology directly reflects its function. A large number of molecules have been described in spines, involving several biochemical families. Considering the small size of a spine, the variety of molecules found is astounding, suggesting that spines are paramount examples of biological nanotechnology. Single-molecular studies appear necessary for future progress. The purpose of this rich molecular diversity is still mysterious but endows synapses with a diverse and flexible biochemical machinery.