Immune reconstitution syndrome (IRIS) is a clinical syndrome that has been described in HIV infected patients after initiation of highly active anti-retroviral therapy (HAART), and is characterized by paradoxical acute worsening of an underlying opportunistic infection or AIDS-defining illness. There is no widely accepted syndromic definition, the pathogenesis of the syndrome is unclear and there is no specific therapy. The syndrome is more common in patients with low CD4+ T cell counts (less than 50 cells/microL) and in those with certain underlying infections (e.g. mycobacterial or cryptococcal infection) and is typically observed when there is evidence of response to HAART and while patients are still at risk for other opportunistic infections (OIs) or AIDS defining illnesses (e.g. pneumocystis jirovecii pneumonia or cytomegalovirus [CMV] retinitis). The incidence of IRIS varies depending on the studied population and is very frequent in developing countries creating significant diagnostic and therapeutic challenges as well as utilization of limited health resources.