The central nervous system is composed of neural ensembles, and their activity patterns are neural correlates of cognitive functions. Those ensembles are networks of neurons connected to each other by synapses. Most neurons integrate synaptic signal through a remarkable subcellular structure called spine. Dendritic spines are protrusions whose diverse shapes make them appear as a specific neuronal compartment, and they have been the focus of studies for more than a century. Soon after their first description by Ramón y Cajal, it has been hypothesized that spine morphological changes could modify neuronal connectivity and sustain cognitive abilities. Later studies demonstrated that changes in spine density and morphology occurred in experience-dependent plasticity during development, and in clinical cases of mental retardation. This gave ground for the assumption that dendritic spines are the particular locus of cerebral plasticity. With the discovery of synaptic long-term potentiation, a research program emerged with the aim to establish whether dendritic spine plasticity could explain learning and memory. The development of live imaging methods revealed on the one hand that dendritic spine remodeling is compatible with learning process and, on the other hand, that their long-term stability is compatible with lifelong memories. Furthermore, the study of the mechanisms of spine growth and maintenance shed new light on the rules of plasticity. In behavioral paradigms of memory, spine formation or elimination and morphological changes were found to correlate with learning. In a last critical step, recent experiments have provided evidence that dendritic spines play a causal role in learning and memory.