The use of highly active antiretroviral therapy (HAART) in the management of human immunodeficiency virus (HIV) restores immune responses against pathogens and has greatly decreased mortality. However, in about 25% to 35% of patients receiving HAART, the reconstituted immune system leads to a pathological inflammatory response, commonly known as immune reconstitution inflammatory syndrome (IRIS), which causes substantial short-term morbidity or even mortality. Although we have gleaned some knowledge on IRIS in the past few years, a number of unanswered questions remain. In this review, we discuss the definition, diagnostic criteria, pathogenesis, risk factors, clinical spectrum including oral manifestations, and management of IRIS.