Cryoablation induces cellular damage mainly via disruption of membranous organelles, such that destruction to the gross myocardial architectures is reduced. Cryoablation destroys tissue by removing heat from it via a probe that is cooled down to freezing temperatures, which has been made feasible by the invention of refrigerants that permit ultra-effective cooling. Freezing results in both immediate and delayed damage to the targeted tissue. Immediate effects include hypothermic stress and direct cell injury, while delayed consequences are the results of vascular-mediated injury and apoptotic cell death. The histological effect of cryoablation can be divided into three phases: the immediate postthaw phase, hemorrhagic and inflammatory phase, and replacement fibrosis phase. The chapter summarizes the factors affecting cryoablation efficacy. With better defined catheters and freezing parameters based on ablation outcomes, and the development of new cryogens and delivery systems, the safety and efficacy profiles of cryoablation will continue to improve.