Purpose of reviewThe rabbit polyclonal, antithymocyte, antibody Thymoglobulin is used as a potent T-cell depleting agent in immunosuppression for more than 30 years. New findings continuously expand our understanding of the immunopharmacology of Thymoglobulin and translate into novel therapeutic concepts.Recent findingsIn vitroandin vivostudies have shown that Thymoglobulin acts both in the blood and in secondary lymphoid organs. The action is rapid because the binding to cell surface molecules does not require new gene expression. Apoptotic cell death was identified as the main pathway for cell depletion in lymphoid organs. Functional cellular changes are primarily induced by modulation of cell surface antigens. The ability of Thymoglobulin to interfere with leukocyte–endothelium interactions by both downmodulating adhesion molecules and binding to chemokine receptors has recently been demonstrated. Significant depletion and modulation can both be achieved by short-term and high-dose regimens and are used now in induction therapies to effectively reduce immunosuppressive maintenance therapies. Long-term studies have shown characteristic changes associated with the short-term therapy persisting for years. These changes reflect age-dependent regeneration pathways and subset-specific kinetics.SummaryRecent studies provide new insights into the mechanisms of action unique to Thymoglobulin as a polyclonal antibody preparation. In particular, they identify the key role of drug-dosing regimens for the optimal use of nonspecific and specific immunomodulating actions.