Contrary to common psychosurgical practice in the 1950s, Dr. Jean Talairach had the intuition, based on clinical experience, that the brain connectome and neuroplasticity had a role to play in psychosurgery. Due to the remarkable progress of pharmacology at that time and to the technical limits of neurosurgery, these concepts were not put into practice. Currently, these concepts are being confirmed by modern techniques such as neuroimaging and computational neurosciences, and could pave the way for therapeutic innovation in psychiatry. Psychosurgery commonly uses a localizationist approach, based on the idea that a lesion to a specific area is responsible for a deficit opposite to its function. To psychosurgeons such as Walter Freeman, who performed extensive lesions causing apparently inevitable deficit, Talairach answered with clinical data: complex psychic functions cannot be described that simply, because the same lesion does not provoke the same deficit in different patients. Moreover, cognitive impairment did not always follow efficacious psychosurgery. Talairach suggested that selectively destructing part of a network could open the door to a new organization, and that early psychotherapy could encourage this psychoplasticity. Talairach did not have the opportunity to put these concepts into practice in psychiatric diseases because of the sudden availability of neuroleptics, but connectomics and neuroplasticity gave rise to major advances in intraparenchymal neurosurgery, from epilepsy to low-grade glioma. In psychiatry, alongside long-standing theories implicating focal lesions and diffuse pathological processes, neuroimaging techniques are currently being developed. In mentally healthy individuals, combining diffusion tensor imaging with functional MRI, magnetoencephalography, and electroencephalography allows the determination of a comprehensive map of neural connections in the brain on many spatial scales, the so-called connectome. Ultimately, global neurocomputational models could predict physiological activity, behavior, and subjective feeling, and describe neuropsychiatric disorders. Connectomic studies comparing psychiatric patients with controls have already confirmed the early intuitions of Talairach. As a striking example, massive dysconnectivity has been found in schizophrenia, leading some authors to propose a "dysconnection hypothesis." Alterations of the connectome have also been demonstrated in obsessive-compulsive disorder and depression. Furthermore, normalization of the functional dysconnectivity has been observed following clinical improvement in several therapeutic interventions, from psychotherapy to pharmacological treatments. Provided that mental disorders result from abnormal structural or functional wiring, targeted psychosurgery would require that one be able: 1) to identify the pathological network involved in a given patient; 2) to use neurostimulation to safely create a reversible and durable alteration, mimicking a lesion, in a network compatible with neuroplasticity; and 3) to predict which functional lesion would result in adapted neuronal plasticity and/or to guide neuronal plasticity to promote recovery. All these conditions, already suggested by Talairach, could now be achievable considering modern biomarkers and surgical progress.