Antiretroviral therapy (ART), which is intended to inhibit HIV replication, promotes partial restoration or activation of immunity. In many patients who have severe immunosuppression, ART may increase the risk of development of immune restoration syndrome (IRS), which is associated with the manifestations of opportunistic and secondary diseases that lead to worsening of the general health of patients and to their death. The present paper addresses IRS-related terminology, the risk factors of IRS development, and IRS pathogenesis, epidemiology, and clinical and laboratory manifestations. Special attention is paid to secondary and opportunistic infections associated with IRS and to the possibilities of pharmacotherapy for IRS and its complications. Characteristic radiological manifestations of brain lesions upon IRS are described as they as associated with different pathogenic factors upon initially poor immunity. It is hard to assess IRS incidence in Russia: IRS is diagnosed seldom because of the ambiguity of its clinical picture. A combination of the main clinical and laboratory manifestations of the syndrome is suggested to help in IRS diagnosis. IRS prevention is based on reasonable regiments of ART following preventing therapy for possible manifested infections and also on early ART onset upon steady CD4 cell counts and low HIV RNA blood levels.