BACKGROUND: Stereoelectroencephalography (SEEG) was developed by Talairach and Bancaud in Paris in the late 1950s. Subsequently, the Talairach methodology was adopted at a number of additional centers in Europe and Canada. Technical aspects remained essentially unchanged for the following 30 years. Only in the last two decades, because of advancements in image-guided surgery systems, robotics, and computer-aided planning, use of SEEG has become more widespread, and reports describing these new developments have been published. OBJECTIVES: This systematic review was designed to assess published reports of SEEG surgical techniques and safety profile. DATA SOURCES: An electronic search was performed of Medline, Embase, and Scopus databases. In addition, the content pages of several standard epilepsy surgery textbooks were searched. Full-text English studies describing SEEG surgical technique or pertinent epidemiological data were included. Conference abstracts, reviews, posters, editorials, comments, and letters were excluded. RESULTS: Three hundred fifty-nine of 2,903 potentially eligible studies published by 32 centers were reviewed. Thirty-one of these primarily discussed the surgical technique. Thirty-five major complications (including 4 fatalities) were reported among 4,000 patients (0.8%) implanted with 33,000 electrodes. LIMITATIONS: The number of SEEG patients is likely to be underestimated because only a few groups have exhaustively reported their experience. Moreover, it is possible that a number of teams performing SEEG have not published studies on the topic. CONCLUSIONS: Rigorous SEEG, thanks to its basic principles and updated technologies, is a safe and accurate method to define the epileptogenic zone by means of stereotactically implanted intracerebral electrodes.