Tissue ablation is an essential procedure for the treatment of many diseases. In the last decade, a nonthermal tissue ablation using intensive pulsed electric fields, called nonthermal irreversible electroporation (NTIRE), has rapidly emerged. The exact mechanisms responsible for cell death by NTIRE, however, are currently unknown. Nevertheless, the technique's remarkable ability to ablate tissue in the proximity of larger blood vessels, to preserve tissue architecture, short procedure duration, and shortened postoperative recovery period rapidly moved NTIRE from bench to bed side. This work provides an overview on the development of NTIRE, its current state-of-the-art, challenges, and future needs.