Kawasaki syndrome (KS) is one of the most common causes of acquired heart disease in children (reviewed in [1, 2]). Since its first description in 1967 , there have been substantial advances in our understanding of its epidemiology and approaches to its treatment. In particular, the introduction of high-dose intravenous immunoglobulin (IVIG) treatment, within the first 10 days after the onset of fever, has significantly reduced the prevalence of coronary artery abnormalities in KS [4-6]. Early recognition and prompt treatment of this illness is, therefore, important. Unfortunately the diagnosis of acute KS is currently based exclusively on clinical criteria, using clinical features which overlap with a number of other illnesses, and can, therefore, create diagnostic dilemmas in atypical cases (Table 1). The development of an objective diagnostic test will probably require identification of the etiological agent. Recent insights into the immunopathogenesis of acute KS combined with microbiological studies support the concept that the acute clinical complex associated with this illness is triggered by staphylococcal or streptococcal toxins with superantigenic properties. These studies provide hope that the cause of this fascinating illness may soon be elucidated and lead to the development of more objective diagnostic tests and effective treatments for this potentially devastating childhood disease. The current review examines the clinical, immunological and epidemiological studies which support the hypothesis that bacterial superantigens play a role in the pathogenesis of acute KS.