Superantigens belong to a small family of proteins capable of inducing T-cell activation and proliferation. They are produced by retrovirus encoded genes or by bacteria. Bacterial products are responsible for the pathogenicity of infections, such as in the case of toxic shock syndrome. Superantigens differ from antigens and mitogens by their capacity to activate limited subsets of T-cells expressing defined V8 chains of the T-cell receptor. They require presentation by antigen presenting cells and are generally not processed before presentation. Superantigens bind to major histocompatibility class II molecules to a site that is different from the peptide binding site. They interact with the V8 chain on the T-cell receptor. In contrast to antigens, they are unable to induce memory T-cells. Activation by Superantigens results in clonal expansion of the responding T-cells and by their massive deletion, whereas the remaining T-cells become  anergic to a challenge by the same superantigen. Our understanding of the mechanisms involved in T-cell repertoire selection and in cellular anergy is largely due to the utilisation of these molecules. Superantigens have served as valuable tools to follow the fate of activated T-cells in vivo and in vitro. Three-dimensional structures of superantigens bound to major histocompatibility class II molecule or the V8 chain of the TCR are now available. In this article we review information on the physiological effects of superantigens and on the mechanisms involved in superantigen recognition by major histocompatibility class II molecules and T-cell receptor.