Hemispheric specialization (HS), or hemispheric dominance, is a nineteenth century concept that relates to the fact that a given hemisphere is the pilot of a given function such as, for example, the left hemisphere is dominant for language and for right-handedness. HS is grounded in both intra-hemispheric white matter connections, supported by associative bundles, and inter-hemispheric connections between cortical areas located in mirrored positions (homotopic), through the corpus callosum (CC) fiber tracts. Imaging investigations have measured anatomical and/or functional asymmetry, assessing HS at the voxelwise, regional, or hemispheric level. Comparison of these simple measures obtained with functional imaging during language tasks with results from the Wada test has validated that asymmetries do size up HS and pave the way for the investigation of HS in healthy humans. Anatomical asymmetries explain only a fraction of functional variability in lateralization, likely because structural and functional asymmetries develop at different periods of life. Anatomical asymmetries appear as early as the 26th week of gestation; at birth they are identical to those of adults. In contrast, functional neuroimaging investigations have revealed that inter-hemispheric connectivity appears at birth and is leftward asymmetrical in auditory areas, whereas in highorder language areas, this inter-hemispheric connectivity slowly shifts during development to a predominant intra-hemispheric connectivity in the adult. The precise timing and neural basis of this shift are still unknown, but it has been nevertheless shown that the connectivity is not yet in place at the age of seven and that it parallels an increase in leftward asymmetry during language tasks. Abnormal development of this asymmetry is observed in severe mental illnesses that exhibit language symptoms, such as schizophrenia and autism. In addition, after a dominant hemisphere lesion, good language capacities are associated with the recovery of a leftward asymmetry during language tasks. However, neuroimaging studies have shown that HS variability for language, up to rightward dominance, exists in healthy individuals and is partly explained by both behavioral (handedness) and anatomical (i.e., brain volume, size of the left planum temporale) factors, with these factors possibly interacting with one another. Knowledge of the setting up of N. Tzourio-Mazoyer (*)