This research article explores the ancient origins of trepanation, unravelling its early instances and the associated cultural beliefs that have shaped cranial surgery. It scrutinises the medieval and Renaissance periods, elucidating the evolution of trepanation techniques within the context of advancements in medical knowledge and societal changes. In addition, the research investigates the diverse practices of trepanation across cultures, offering insights into the unique approaches, beliefs and rituals associated with this ancient surgical procedure. Examining the decline of trepanation in mainstream medicine, the article assesses the factors contributing to its diminishing prevalence and the emergence of alternative surgical methods. The study also delves into sporadic resurgences of trepanation in unconventional contexts, providing a nuanced understanding of its enduring fascination. In exploring trepanation’s impact on modern medicine, the article sheds light on its contributions to the study of cranial anatomy, the evolution of surgical tools and the broader narrative of medical progress. Ultimately, this historical investigation contributes to a comprehensive understanding of trepanation, revealing the intricate interplay between medicine, culture and the human quest for knowledge and healing.