Learning is associated with structural changes in the human brain that can be seen and studied by MRI. These changes are observed in gray matter and surprisingly also in white matter tissue. Learning a wide range of skills, from sports, computer games, music, and reading, to abstract intellectual learning, including classroom study, is associated with structural changes in appropriate cortical regions or fiber tracts. The cellular changes underlying modifications of brain tissue during learning include changes in neuronal and glial morphology as well as vascular changes. Both alterations in axon morphology and myelination are thought to contribute to white matter plasticity during learning but to varying degrees depending on age. Structural changes in white matter could promote learning by improving the speed or synchrony of impulse transmission between cortical regions mediating the behavior. Action potentials can stimulate oligodendrocyte development and myelination by at least three known mechanisms that involve signaling molecules between axons and oligodendrocytes, which do not require neurotransmitter release from synapses. Integrating information from cellular/molecular and systems-level research on normal cognitive function, development, and learning is providing new insights into the biological mechanisms of learning and the structural changes produced in the brain.