The immune reconstitution inflammatory syndrome (IRIS) represents a heterogeneous group of conditions. Whilst they typically present in HIV-infected patients with advanced immunodeficiency, IRIS have also been described in HIV-negative patients with immune reconstitution due to other causes of immunosuppression. Frequently IRIS results from an immune response against underlying infection (pathogen-associated IRIS). However, IRIS might become evident during immune reconstitution without an underlying pathogen such as a sarcoid-like illness or an autoimmune thyropathy. Here we report on the epidemiology and risk factors of IRIS along with diagnosis and management of this clinically important inflammatory syndrome.