Despite the success of immunosuppressive drug therapy to reduce the incidence of acute rejection in organ transplantation, chronic rejection is still an impediment to long-term graft survival and tolerance. There is a growing body of evidence that B-cell production of alloantibody is an important element in the genesis of chronic rejection. Effector function of B cells in transplantation is not specifically targeted by current T-cell-directed therapeutic approaches. We briefly discuss the origin, animal models, diagnostic methods, and currently available B cell reagents that might be used in combination with existing immunosuppressive regimens to address B-cell-mediated allograft injury.