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Necrosis is an in vivo chaotic event distinguished by uncontrolled disintegration of the cell membrane leading to cytolysis, inflammation and tissue destruction followed by a healing or regenerating process. Targeting necrosis may offer potential diagnostic, therapeutic and/or theragnostic applications in translational medicine. This article reviews the current concept of necrosis including definition, etiology and pathophysiology. The evolution and development of a wide diversity of necrosis targeting agents and their potential applications in preclinical and clinical settings are also elaborated and discussed.