The United States Army Research Institute of Environmental Medicine (USARIEM) celebrated its 50th anniversary on July 1, 2011. This article reviews its history, evolution, and transition of its research programs as well as its scientific and military accomplishments, emphasizing the past 25 yr. During the 1990s, USARIEM published a series of pocket guides providing guidance for sustaining Warfighter health and performance in Southwest Asia, Somalia, the former Republic of Yugoslavia, Rwanda, and Haiti. Issues identified during Operation Desert Storm elicited research that improved nutritional guidelines for protracted desert operations; safer use of nuclear, chemical, and biological protective clothing; equipment, development, and fielding of efficient microclimate cooling systems; and effective evaluation of pharmaceuticals to protect soldiers from chemical and biological threats. During the first decade of the 21st century, USARIEM and the Department of the Army published official medical/performance doctrines for operations in the heat and cold and at high altitude. The current Global War on Terrorism focused research to improve doctrines for hot, cold, and high-altitude operations, reduce musculoskeletal training injuries, provide improved field nutrition, more efficient planning for operational water requirements, and improve both military clothing and materiel. This article also describes the critically important interactions and communications between USARIEM and deployed units and the benefits to Warfighters from this association. This report presents USARIEM's unique and world-class facilities, organizational changes, scientific and support personnel, and major research accomplishments, including the publication of 2,200 scientific papers over the past 25 yr. (Contains 1 figure.)