Mass exposure to radiation does not occur frequently but such events, when they do occur, present tremendous challenges to affected communities. With the concerns of recent years about nuclear or radiological terrorism, it would also appear that the risk of deliberate mass exposures to radiation has increased. Nuclear power plant accidents leading to the release of radioactive materials could cause widespread environmental contamination with a variety of radionuclides. This chapter summarizes the prompt and delayed effects of fission explosions in the range of energy yields expected from an improvised nuclear device. The acute radiation syndrome (ARS) encompasses a set of complex pathophysiological processes precipitated by exposure to high doses of radiation. The major determinant of clinical outcome following an acute radiation exposure is the dose received by the affected individual. Estimating this dose (in a process termed biodosimetry) thus becomes a critical part of clinical management of such individuals.