Instrument separation during endodontic therapy is a frequent accident with rotary instruments being more likely to separate than manual ones. The treatment of cases with a separated instrument can be either conservative or surgical. A conservative approach involves the following treatment choices: a) bypass of the fragment, b) removal of the fragment, c) instrumentation and obturation coronally to the fragment. Concerning the removal of a separated instrument, a variety of techniques and systems have been developed. Ultrasonics, in combination with the operative microscope constitute the most effective and reliable tools for removing a separated endodontic instrument from a root canal. The likelihood of successful removal depends on: the level of separation (coronal, middle or apical third); location in relation to the root canal curvature; the type of separated instrument; its length; the degree of canal curvature and the tooth type. Several complications may occur during the management of a separated instrument: separation of the ultrasonic tip or file used for bypassing or removing the instrument; further separation of the fragment; perforation; ledge; extrusion of the file into periapical tissues; tooth weakening due to dentin removal, as well as excessive temperature rise in periodontal tissues. Prognosis for a tooth retaining a separated instrument depends on the presence of a periapical lesion, the microbial load of the root canal during the time of separation and the quality of the obturation.