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Background: There is a dearth of published information on the posterior perforated substance as compared to the anterior perforated substance. We managed to glean facts about the posterior perforated substance that can serve as a landmark for surgical operations in the adjacent regions of the midbrain and the vessels passing through it. Moreover, the posterior perforated substance contains the interpeduncular nucleus responsible for the mental state of the individual., Objectives: 1) To describe the topography of the blood vessels supplying the posterior perforated substance area from the surgical point of view; 2) to investigate the functions of the interpeduncular nucleus., Methods: We assembled and analyzed results from source databases by Elsevier, NCBI MedLine, Scopus, Scholar. Google and Embase. Each article was studied in detail for practically useful information about the posterior perforated substance., Results: The P1-segment perforating branches of the posterior cerebral artery supply the posterior perforated substance. This area is especially vulnerable in the case of vascular pathologies. The posterior communicating artery can block the surgeon's view and impede maneuverability of the tool in the area of the posterior perforated substance, which may be addressed using the separation technique, which can lead to positive results. In addition, the medial habenula-interpeduncular nucleus in the posterior perforated substance is associated with various addictions and psychiatric conditions., Conclusion: The posterior perforated substance area is of great interest for surgical interventions. Future studies of the interpeduncular nucleus anticipate the development of drugs to affect different types of dependencies and some mental diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)