The adult brain has long been viewed as a collection of neuronal networks that maintain a fixed configuration of synaptic connections. Brain plasticity and learning was thought to depend exclusively on changes in the gain and offset of these connections. Over the last 50 years, molecular and cellular studies of neuroplasticity have altered this view. Brain plasticity is now viewed as a continuum of structural changes that could vary from long-range axon growth to the twitching of dendritic spines and synaptic receptor composition dynamics. Plasticity proteins similar to those that drive neuronal development may underpin brain plasticity, and consequently could regulate adaptations to new experiences and learning. In vivo imaging has confirmed that neuronal plasticity in the adult brain involves subtle structural changes at synaptic connections, including synapse formation and pruning. Synaptic structural changes are associated with experience-dependent plasticity, learning, brain traumas and neurodegeneration. Owing to the expanding toolbox of in vivo imaging we have come to the brink of understanding the causal relationship between structural synaptic network dynamics and functional brain plasticity. This review summarizes the technical developments in the imaging of laboratory animals' brains in vivo and the insights they have provided into the mechanisms of brain plasticity and learning.