The immune reconstitution inflammatory syndrome (IRIS) is a frequent early complication of antiretroviral therapy (ART) in patients with advanced HIV. Because there is no confirmatory diagnostic test, the diagnosis is based on clinical presentation and exclusion of alternative causes for deterioration, such as antimicrobial drug resistance. Opportunistic infection treatment should be optimized. Mild cases may require symptomatic therapy alone or nonsteroidal anti-inflammatory drugs. Corticosteroids have been used to treat more severe cases of IRIS associated with mycobacterial and fungal infections. There is evidence from a randomized controlled trial that prednisone reduces morbidity and improves symptoms in paradoxical tuberculosis (TB)-IRIS. Neurological TB-IRIS is potentially life-threatening; high-dose corticosteroids are indicated and ART interruption should be considered if level of consciousness is depressed. When considering corticosteroid treatment clinicians should be aware of their side effects and only use them when the diagnosis of IRIS is certain. In viral forms of IRIS corticosteroids are generally avoided.