Recent studies indicate that microtubules (MTs) may play an important role in spine development and dynamics. Several imaging studies have now documented the exploration of dendritic spines by dynamic MTs in an activity-dependent manner. Furthermore, it was found that alterations of MT dynamics by pharmacological and molecular approaches exert profound influence on the development and plasticity of spines associated with neuronal activity. It is reasonable to speculate that dynamic MTs may be responsible for targeted delivery of specific cargos to a selected number of spines and/or for interacting with the actin cytoskeleton to generate the structural changes of spines associated with synaptic modifications.