Cryosurgery is a method of achieving lesion destruction by rapid freezing in situ. Application of cryosurgery in medicine widespread and its use within dentistry is also well documented, using both open and closed liquid nitrogen and carbon dioxide. The major advantages of oral cryosurgery include bloodless treatment, very low incidence of secondary infection, and a relative lack of scarring and pain. This review outlines knowledge on the mechanisms, tissue response, and current practices of cryosurgery in the oral and peri-oral region. More experimental studies are needed to better understand this important modality at cellular and molecular levels. Inconsistency in the current protocols used for the treatment of the oral lesions is evident. Additional studies are needed to define the treatment protocols for different types of oral lesions. Information on the cryogen type and dose and the delivery technique required would help to produce reproducible outcomes for the treatment of targeted lesions.