The corpus callosum is the largest fibre tract in the human brain and subserves many of the brain’s higher-order functions. Disconnection syndromes resulting from surgical ablation, developmental absence (agenesis of the corpus callosum), disease, or injury of the corpus callosum can have profound consequences on cognition. Callosal development involves an intricate series of sequential and concurrent processes, including telencephalic induction, midline tissue patterning, production and specification of callosal neurons. In addition, axon extension and long-range axonal guidance from one hemisphere to the other are required for functional circuit formation in the contralateral hemisphere. Genetic or traumatic disruption to any part of this sequence is pathogenic. Understanding the key processes involved in callosal development is the first step in providing both better neuropsychological outcomes and improved diagnostic and prognostic tools for congenital disconnection syndromes in the future.