Superantigens include bacterial products (mainly of streptococci and staphylococci) that stimulate T cells to proliferate nonspecifically through interaction with class II major histocompatibility complex products on antigen-presenting cells and then with variable regions on the beta chain of the T cell receptor complex. They include pyrogenic toxins (streptococcal scarlet fever toxins of serotypes A, B, and C, toxic shock syndrome toxin 1, and staphylococcal enterotoxin serotypes A, B, Cn, D, E, and G), streptococcal M protein, staphylococcal exfoliative toxin, and recently identified pyrogenic toxins made by groups B, C, F, and G streptococci and Streptococcus sanguis. Pyrogenic toxin superantigens cause acute toxic shock syndrome and are associated with toxic shock-like syndromes. Superantigens cause symptoms via release of immune cytokines. These proteins should be considered potential causes of illnesses such as rheumatic fever, arthritis, Kawasaki syndrome, atopic dermatitis, and guttate psoriasis because of their potent immune system-altering capacity.