Tumor necrosis factor receptor 2 (TNFR2), also known as tumor necrosis factor receptor superfamily member 1B (TNFRSF1B), is a transmembrane protein, which can mediate both pro- and anti-inflammatory activities of T cells. TNFR2 is mainly expressed on the surface of activated effector T cells and regulatory T cells (Tregs) and promotes proliferation and survival of Tregs through nuclear factor kappa B (NF-κB). Blockade of TNF-TNFR2 interaction with monoclonal antibodies can inhibit the activation of Tregs, possibly resulting in inhibition of their function and/or reduction of their numbers. Yet, until recently the potential of TNFR2 as a therapeutic target for cancer therapy has been underappreciated.