Toxic shock syndrome is a rare, life-threatening disease caused by Staphylococcus aureus or Streptococcus pyogenes. These bacteria are able to produce superantigens, which bypass normal antigen presentation and cause a clonal T-cell expansion and uncontrolled release of pro-inflammatory mediators, which results in severe multiple organ failure. Despite high morbidity and mortality, the disease is underdiagnosed. In order to reduce morbidity and mortality early diagnosis and treatment with a combination of beta-lactam antibiotics, clindamycin and intravenous immunoglobulin is essential, which is underlined in this review.