Microbial superantigens are a family of protein exotoxins that share the ability to trigger excessive and aberrant activation of T cells. The best characterised are the staphylococcal enterotoxins and the streptococcal pyrogenic exotoxins that trigger the staphylococcal and streptococcal toxic shock syndromes. It is now apparent that superantigens have a wider role in the pathology of infectious diseases than has previously been appreciated. Staphylococcus aureus and Streptococcus pyogenes together produce 19 different superantigens. The range of microorganisms known to produce superantigens has expanded to include Gram negative bacteria, mycoplasma, and viruses. Research is beginning to shed light on the more subtle parts these molecules play in causing disease and to produce some real possibilities for specific treatment of superantigen-induced toxicity. We aim to highlight these new developments and review the science behind these fascinating molecules.