The study of possible mechanisms resulting in changes in the immune system after exposure to ionizing radiation is an area that has not been thoroughly evaluated during recent years. This article presents an overview of immunological monitoring studies of personnel from the radiation-hazardous factories that took place over the past 20 years in Russia. The methodology of these studies is based on: (1) the preclinical evaluation of immune status of workers whose occupation involves potential exposure to ionizing radiation; (2) selecting at risk groups according to the nature of immune deficiency manifestation; and (3) studying the changes of immune status of employees with regard to the potential effects of radiation exposure. The principal aim of these studies is accumulation of new data on the impact of radiation exposure on the human immune system and search for the relationship between the clinical manifestations of immune disorders and laboratory parameters of immunity to improve the monitoring system of the health status of the professional workers involved in radiation-hazardous industrial environments and the population living close to these facilities.