Instrument separation is a common complication in endodontic treatment, and its prognosis depends on multiple factors, including the periapical status and the location of the separated instrument. In teeth with vital pulp or without periapical lesions, retaining the instrument followed by careful root canal obturation generally results in a favorable prognosis. In contrast, for infected canals or those with periapical periodontitis, instrument removal and, when necessary, endodontic surgical intervention are more clinically significant. With the development of advanced techniques such as dental microscopy, ultrasonics, cone-beam computed tomography (CBCT), and artificial intelligence, the diagnosis and management of separated instruments have become increasingly precise. Nevertheless, further evidence-based research is required. This article analyzes and summarizes the existing evidence in combination with clinical experience to provide a reference for clinical decision-making.