The mode of action of rabbit antithymocyte globulin (rATG) includes preferential inhibition of pre-existing donor-reactive memory T-cell reconstitution and possibly apoptosis of plasma cells, the source of donor specific antibodies (DSAs). In kidney transplant patients with low-strength preformed DSAs, non-comparative data have shown a low incidence of antibody-mediated rejection (ABMR) and graft survival using rATG even without desensitization procedures. For high strengths of preformed DSAs, rATG induction with more aggressive desensitization appears effective, with mixed results concerning the addition of B-cell specific agents. Regarding production of de novo DSA (dnDSA), interpretation of retrospective analyses is limited by selective use of rATG in higher-risk patients. Observational data in moderately sensitized kidney transplant patients suggest that the incidence of dnDSA and ABMR is significantly lower with rATG versus basiliximab. A randomized pilot study has suggested that addition of rituximab or bortezomib may not further inhibit dnDSA production in rATG-treated patients. Overall, rATG appears to inhibit DSA production, with a potential role in reducing the risk of ABMR in kidney transplant patients with high-strength preformed DSA, or lowering dnDSA in moderately sensitized patients. Randomized trials are awaited.