The use of antiretroviral therapy (ART) to treat HIV infection, by restoring CD4+ cell count and immune function, is associated with significant reductions in morbidity and mortality. Soon after ART initiation, there is a rapid phase of restoration of pathogen-specific immunity. In certain patients, this results in inflammatory responses that may result in clinical deterioration known as 'the immune reconstitution inflammatory syndrome' (IRIS). IRIS may be targeted at viable infective antigens, dead or dying infective antigens, host antigens, tumour antigens and other antigens, giving rise to a heterogeneous range of clinical manifestations. The commonest forms of IRIS are associated with mycobacterial infections, fungi and herpes viruses. In most patients, ART should be continued and treatment for the associated condition optimized, and there is anecdotal evidence for the use of corticosteroids in patients who are severely affected. In this review, we discuss research relating to pathogenesis, the range of clinical manifestations, treatment options and prevention issues.