Reactive arthritis is an infectious disease which may be initiated by several microbes in genetically susceptible hosts. The best known predisposing genetic factor is HLA-B27, but the mechanisms behind its action are still elusive. Worldwide agreement exists regarding the general guidelines in the diagnosis, differential diagnosis and management, even though official diagnostic criteria are not yet available. Several studies indicate that antibiotics are effective only if started before the immunological mechanisms of pathogenesis have been turned on. However, recent observations suggest that a 3-month course of antibiotics may diminish the late risk of chronic sequelae, especially in HLA-B27-positive patients with reactive arthritis.