Cryotherapy or cryoablation involves the freezing of tissues to destroy unwanted tissue or to control bleeding. Endoscopic cryotherapy has been developed for gastrointestinal application by through-the-scope noncontact delivery of compressed carbon dioxide gas or liquid nitrogen (cryospray) or contact balloon cryoablation. The mechanism of cryotherapy ablative effects includes immediate injury as well as coagulation necrosis occurring over several hours and days, unlike heat-based thermal ablation. This article reviews the basis, technique, safety, efficacy, and durability for the use of endoscopic cryotherapy in Barrett’s esophagus and esophageal adenocarcinoma.