Staphylococcal protein A (SPA), HIV gp120, and staphylococcal enterotoxins (SE) are B cell superantigens that induce VH specific B cell responses. In addition, the red blood cell antigens, i/I, have some features of a B cell superantigen. Binding of SPA, SE and HIV gp120 are VH family specific, whereas binding of i/I is VH gene specific. SPA and HIV gp120 function by stimulating VH3-expressing B cells, whereas SE appear to function by enhancing survival of the appropriate VH-expressing B cells. Moreover, HIV gp120 has been shown to delete VH3-expressing B cells. In this review, we describe evidence that shows how these superantigens may play a role in shaping the normal B cell repertoire.