The B7 family of T-cell costimulatory molecules has expanded considerably in recent years. Among the new costimulatory molecules discovered are inhibitory and activating pathways. Both ligands and receptors often have multiple binding partners, adding to the complexity of T-cell regulation. Some B7 molecules also exhibit reverse signaling, affecting activation of both antigen-presenting cells and T cells. An increased understanding of these pathways of T-cell regulation results in promising new therapeutics because T-cell interference can be better targeted to specific states of activation or location. This will decrease side-effects such as systemic immunosuppression and increase efficiency. Targeting B7 molecular pathways for either inhibiting or increasing cell-mediated immunity has so far shown promising results in models of autoimmunity, transplant rejection and tumor immunotherapy.