Dendritic spines are tiny protrusions that receive excitatory synaptic input and compartmentalize postsynaptic responses. Heterogeneous in size and shape, and modifiable by activity and experience, dendritic spines have long been thought to provide a morphological basis for synaptic plasticity. Although advanced imaging techniques have highlighted the rapid and regulated motility of spines in living neurons, the functional significance of spine plasticity remains elusive. Recent insights into the molecular mechanisms that regulate spine morphogenesis offer potential ways to manipulate dendritic spines in vivo and to explore their physiological roles in the brain.