Antiretroviral therapy (ART) inhibits HIV replication, allowing recovery of CD4+ T cell numbers and the restoration of immune function; its introduction has led to improved outcomes for individuals with HIV infection. However, it has been observed that some individuals responding to ART experience a clinical deterioration with symptoms and signs of an inflammatory illness. Immune reconstitution inflammatory syndrome (IRIS) results from pathological immune responses occurring during immune reconstitution. IRIS is best considered a group of disorders with a wide range of clinical manifestations, incorporating disease resulting from pathological inflammation to pathogens, immune-mediated inflammatory disease and autoimmune disease. Clinical effects range from a mild, self-limiting illness to severe morbidity and mortality. Clinicians working in the field of HIV medicine can expect to encounter individuals with IRIS. In this review, we discuss definitions, describe clinical presentations, summarize research relating to pathogenesis and identify risk factors, preventive and management strategies.