With studies elucidating the cytokine programs associated with T-cell activation, allograft rejection and tolerance induction, the Th1/Th2 paradigm has become a unifying model to explain the observed cytokine profiles. The proof that these cytokines mediate allograft tolerance, however, is at best indirect. More recent studies highlighting the redundant and pleiotropic nature of cytokine networks suggest that the Th1/Th2 paradigm may not be sufficient to explain fully the mechanisms underlying allograft tolerance.