Crush syndrome is a fine example of how pathology can play a direct role in revealing the best treatment and management for diseases. It can occur when crush injuries are sustained. Skeletal muscle becomes damaged under the weight of a heavy object, and victims experience severe shock and renal failure. The discovery of the pathology of crush syndrome belongs to two individuals: Seigo Minami and Eric Bywaters. They separately helped to define the pathogenesis of crush syndrome during World Wars I and II. Seigo Minami is believed to have been the first to record the pathogenesis of crush syndrome. In 1923, he described the cases of three soldiers who died of renal failure caused by crush injury during World War I. Using microscopic studies to investigate the pathology of their kidneys, he found the soldiers had died due to ‘autointoxication’ caused by rhabdomyolysis. This discovery was not known to Eric Bywaters, who described crush syndrome in 1941, having studied victims of the London Blitz during World War II. He defined the ‘autointoxication’ as the release of rhabdomyolysis products via reperfusion. He therefore established the need for emergency fluid replacement to treat crush syndrome. The findings made by Minami and Bywaters highlight a remarkable achievement in clinical pathology, despite the adversity of war. It is these findings on which current guidelines are based. By reviewing their work, it is hoped that the role of pathology can be better appreciated as a valuable resource for delineating the treatment and management of diseases.