Costimulation is critical to T cell activation. On the antigen-presenting cell the key players are found in the extended family of B7 genes comprising cd80, cd86, B7h/B7RP-1 and B7-H1. cd80 and cd86 encode proteins that bind to CD28 and CTLA4 on T cells. Blocking this pathway with the potent CTLA4-Ig fusion protein shows encouraging potential as a therapeutic agent. While cd80 and cd86 pathways act mainly on naive T cells, B7h/B7RP-1 and B7-H1 seem to exert their effects on antigen-experienced lymphocytes.