Glioblastoma (GB) is the most frequent and aggressive primary tumor of the central nervous system. Prognosis remains poor despite ongoing progress. In cases where the gadolinium-enhanced portion of the GB is completely resected, 90% of recurrences occur at the margin of surgical resection in the macroscopically normal peritumoral brain zone (PBZ). Intratumoral heterogeneity in GB is currently a hot topic in neuro-oncology, and the GB PBZ may be involved in this phenomenon. Indeed, this region, which possesses specific properties, has been less studied than the core of the GB tumor. The high rate of local recurrence in the PBZ and the limited success of targeted therapies against GB demonstrate the need for a better understanding of the PBZ. We present here a review of the literature on the GB PBZ, focusing on its radiological, cellular, and molecular characteristics. We discuss how intraoperative analysis of the PBZ is important for the optimization of surgical resection and the development of targeted therapies against GB.