Toxic shock syndrome (TSS) is an acute, multi-system, toxin-mediated illness, often resulting in multi-organ failure. It represents the most fulminant expression of a spectrum of diseases caused by toxin-producing strains of Staphylococcus aureus and Streptococcus pyogenes (group A streptococcus). The importance of Gram-positive organisms as pathogens is increasing, and TSS is likely to be underdiagnosed in patients with staphylococcal or group A streptococcal infection who present with shock. TSS results from the ability of bacterial toxins to act as superantigens, stimulating immune-cell expansion and rampant cytokine expression in a manner that bypasses normal MHC-restricted antigen processing. A repetitive cycle of cell stimulation and cytokine release results in a cytokine avalanche that causes tissue damage, disseminated intravascular coagulation, and organ dysfunction. Specific therapy focuses on early identification of the illness, source control, and administration on antimicrobial agents including drugs capable of suppressing toxin production (eg, clindamycin, linezolid). Intravenous immunoglobulin has the potential to neutralise superantigen and to mitigate subsequent tissue damage.