Image-guided ablation has evolved rapidly in the past decade into a competitive technique for treating focal solid malignancies. However, as they rely mainly on thermal energy, such as radiofrequency or microwave, many tumors close to sensitive organs, such as ducts, bowel, and nerves, still remain nonablatable owing to the risk of thermal injury. Irreversible electroporation is a novel ablation modality that relies largely on a nonthermal mechanism to induce cell death, and therefore may overcome many of the shortcomings of thermal ablation. Emerging preclinical data as well as early clinical experience is showing promise for this technique in treating a variety of tumors including periportal liver masses, pancreatic cancer, perihilar renal tumors, prostate cancer, and other soft tissue tumors. However, practical limitations remain for irreversible electroporation, and its complete cancer and location-specific safety and efficacy profiles are still largely unknown. We therefore review what is known for this new ablation modality based on preclinical and preliminary clinical data, and discuss its emerging indications as well as technical challenges. [Copyright &y& Elsevier]