Electrolysis and electroporation technologies have been utilized to provide valuable tissue ablation modalities that do not rely on thermal effects as the primary mode of treatment. The synergistic combination of electroporation and electrolysis (commonly referred to as electrolytic electroporation) has provided a new method of tissue ablation that has some distinct advantages over electrolysis or electroporation alone. Electrolysis uses a low-magnitude direct electric current to create chemical species at the electrode-tissue interface which then diffuse through the tissue, resulting in extreme pH changes and cell death. Electroporation, on the other hand, is used to create permeabilizations in the cell membrane that can be used to induce cell death by several different mechanisms: through electrochemotherapy, cytotoxic drugs are introduced to the cell interior, and irreversible electroporation results in cell death by loss of cell homeostasis. When electrolysis is combined with electroporation, a new method of tissue ablation is achieved that results in a very effective method of cell death and may be used to increase the ablation volume, when compared to irreversible electroporation alone. The mechanism of action behind the electrolytic electroporation effect is likely due to the ability of the electrolytic products to penetrate the cell membrane through the permeabilizations created by electroporation. Here, fundamental principles of electrolysis and electroporation are presented, the mechanism of ablation by electrolytic electroporation is discussed, different types of electrolytic electroporation protocols are examined, and early-stage models of the electrolytic effect are introduced. This chapter hopes to serve as a foundation and starting point for further research into this ablation modality as well as for the development of new types of electrolytic electroporation protocols that may be used to address specific clinical needs.