With the advent of novel therapies to directly intervene with B cell immunity and complement activation, antibody-mediated kidney allograft rejection (AMR) has come into the focus of transplant immunologists. Intravenous immunoglobulin, rituximab, bortezomib, and eculizumab have been used to treat patients with acute AMR, apart from the standard treatment of antibody removal with plasma exchange or immunoadsorption and steroid pulses. This article describes the experimental rationale and summarizes the still limited clinical experience with these novel therapies in the transplant setting. Results with the standard treatment for acute AMR, including intense plasmapheresis, intravenous immunoglobulins, and steroids are good with a graft survival of 80% at 18 months. In contrast, patients suffering from chronic AMR have significant irreversible damage in their grafts with substantially impaired graft survival. Thus, the authors propose a step-wise escalation of therapy in refractory cases of acute AMR and advocate an urgent need for controlled therapeutic trials for acute and chronic AMR not to inflict unnecessary harm on our patients by uncontrolled polypragmasy.