Although French psychiatrist-turned-neurosurgeon Jean Talairach (1911–2007) is perhaps best known for the stereotaxic atlas he produced with Pierre Tournoux and Gábor Szikla, he has left his mark on most aspects of modern stereotactic and functional neurosurgery. In the field of psychosurgery, he expressed critique of the practice of prefrontal lobotomy and subsequently was the first to describe the more selective approach using stereotactic bilateral anterior capsulotomy. Turning his attention to stereotaxy, Talairach spearheaded the team at Hôpital Sainte-Anne in the construction of novel stereotaxic apparatus. Cadaveric investigation using these tools and methods resulted in the first human stereotaxic atlas where the use of the anterior and posterior commissures as intracranial reference points was established. This work revolutionized the approach to cerebral localization as well as leading to the development of numerous novel stereotactic interventions by the Sainte-Anne team, including tumor biopsy, interstitial irradiation, thermal ablation, and endonasal procedures. Together with epileptologist Jean Bancaud, Talairach invented the field of stereo-electroencephalography and developed a robust scientific methodology for the assessment and treatment of epilepsy. In this article the authors review Talairach’s career trajectory in its historical context and in view of its impact on modern stereotactic and functional neurosurgery.