The large majority of excitatory synapses are located on dendritic spines which are discrete membrane protrusions present on neuronal dendrites. Interestingly the highly heterogeneous morphology of dendritic spines is thought to be the morphological basis for synaptic plasticity associated to learning and memory formation. Indeed dendritic spines structure is regulated by molecular mechanisms that are fine tuned and adjusted according to level and direction of synaptic activity, development, specific brain region, and different experimental behavioral conditions. This supports the idea that reciprocal changes between the structure and function of spines impact both local and global integration of signals within dendrites. An increasing number of proteins have been found to be morphogens for dendritic spines and provided new insights into the molecular mechanisms regulating spine formation and morphology. Thus determining the mechanisms that regulate spine formation and morphology is essential for understanding the cellular changes that underlie learning and memory in normal and pathological conditions.