Cryoablation refers to all methods of destroying tissue by freezing. Cryoablation causes cellular damage, death, and necrosis of tissues by direct mechanisms (cold-induced injury to cells) and indirect mechanisms (changes to the cellular microenvironment that impair tissue viability). Understanding the relationships between these factors and tumor injury will be critical in the application of future adjuvant therapies to maximize the efficacy of cryoablation and minimize procedural morbidity. Although it is certain that the technologies to perform cryoablation have great potential for evolution, cryoablation of malignancy has already become established as an important modality in image-guided interventional oncology.