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The aim of this review article was to discuss the concept of cryotherapy, its mechanism, physiological effect, and its different applications in the field of endodontics.The selected articles were limited to those published in the English language using the following key words: cryotherapy, cryogenic treatment of nickel-titanium, cold therapy, and cryotherapy in endodontics. The screening of articles was based on an electronic search of the following databases: PubMed, Scopus, Web of Science, and Egyptian Knowledge Bank.The initial search yielded 98 citations, 78 of which were included. On the basis of the collected data, 32 studies addressed the physiological effect of cryotherapy, 10 focused on illustrating a different application of cryotherapy during root canal treatment, and 36 were concerned with the effect of cryogenic treatment on endodontic instruments.It can be concluded that cryotherapy is a simple and cheap supplementary method for minimizing postoperative pain in cases of symptomatic apical periodontitis and for controlling pulpal hemorrhage during vital pulp therapy. Undoubtedly, it is also an indispensable measure for controlling postsurgical swelling and pain after endodontic surgery. However, further studies are needed to clarify the effect of cryogenic treatment of the recent generations of nickel-titanium rotary instruments.