After more than 40 years of clinical renal transplantation, the contribution of humoral immunity to the pathogenesis of allograft rejection is progressively being clarified. With the advent of a new generation of immunosuppressive agents, the production and consequences of anti-donor alloantibodies can now be controlled. In the upcoming years, immunosuppressive regimens that will specifically control both T- and B-cell responses may further improve long-term allograft survival, if the immunosuppressive efficacy of such regimens is not hampered by an increase in infectious, neoplastic or cardio-vascular complications.