Irreversible electroporation (IRE) employs high-voltage electrical pulses for non-thermal image-guided tumor ablation in solid organs. The pulses disrupt the membrane potential of all cells within the ablation zone causing loss of tumour cell homeostasis which results in death. IRE has the advantage of sparing extracellular matrix structures and thereby preserves the anatomical integrity of blood vessels, bile ducts, and ureters. Several prospective phase-I and -II studies demonstrated the safety and cytoreductive efficacy of IRE for the treatment of locally advanced pancreatic, and local prostate tumours. In addition, IRE induces a systemic immune response. When this immune effect can be amplified by combinatory treatment with immunotherapeutic drugs its synergy might form a bridge between local and systemic therapies with potential to develop into a fundamentally new approach to cancer treatment.