Cranial trephination, one of humanity's earliest documented surgical procedures, represents a remarkable intersection of medical practice, ritual belief, and cultural exchange. This study traces the evolution of trephination from the Neolithic through the early medieval period, with particular attention to archaeological and textual evidence from ancient Israel. Drawing on material from Jericho, Lachish, Timna, Akko, Megiddo, Arad, Qarantal, and additional sites, the research demonstrates the persistence of both circular and rectangular trephination techniques. Literary evidence from the Edwin Smith Papyrus, Hippocrates, Celsus, Galen, and Paul of Aegina to the Talmudic Corpus reveals a range of motivations for the procedure, from relieving intracranial pressure after trauma to expelling harmful spirits. Talmudic sources preserve detailed protocols for cranial intervention, including preparatory steps, controlled access to the cranial cavity, and complete removal of offending growths, highlighting parallels between Babylonian and Hellenistic medical traditions. Read alongside the archaeological remains, these texts demonstrate true surgical skill, iterative refinement of instruments, and sophisticated understanding of head injuries and infections. This paper situates trephination at the crossroads of empirical medicine, ritual meaning, and intercultural transmission, illuminating its significance within the broader history and development of ancient neurosurgery and healing traditions in the Eastern Mediterranean.