The immune reconstitution inflammatory syndrome (IRIS) is characterized by clinical deterioration occurring after the initiation of effective antiretroviral therapy (ART) and results from a disordered and exuberant immune response. The syndrome may present as paradoxical IRIS or unmasking IRIS, depending on whether an opportunistic infection was recognized and treated before ART initiation. Numerous descriptions of IRIS caused by many pathogens were published in the years after the introduction of effective ART. In recent years, with enhanced rollout of ART in resource-limited settings, attention has again focused on IRIS because of the enormous burden of opportunistic infections. This review highlights recent findings elucidating risk factors for and the pathogenesis and treatment of IRIS.