Management of high-risk surgical patients with cholecystitis poses a significant clinical problem. These patients are often left with the options of permanent cholecystostomy tube drainage or high-risk surgery. Numerous attempts have been made over the past 4 decades to fulfill the need for a minimally invasive, definitive treatment option for such gallbladder disease. These attempts have largely focused on endoluminal ablation with a variety of sclerosants and have been unable to reliably achieve permanent gallbladder devitalization. The advent of modern percutaneous devices and techniques have provided further opportunity to develop minimally invasive treatment options for high-risk patients. Cryoablation, a thermal ablation modality that induces cell death through tissue freezing, has recently emerged as a promising potential option to treat gallbladder disease. Early studies have demonstrated good technical and clinical success, and a prospective trial is ongoing. This manuscript explains the clinical need for gallbladder cryoablation, briefly revisits historical minimally invasive treatments, describes cryoablation technology and why it is well suited for the gallbladder, and reviews the preclinical and clinical studies evaluating the safety and efficacy of gallbladder cryoablation.