This invention relates generally to the preparation of TRAIL receptor-binding agents and uses of the same. In particular, the present invention relates to the preparation of anti-TRAIL receptor antibodies which recognize a common antigen determinant (i.e., epitope) shared by TRAIL-R1 and TRAIL-R2 receptors and their use for TRAIL receptor detection and modulation of TRAIL receptor-mediated function. The TRAIL receptor-binding agents are useful to induce apoptosis in human cancer cells. These targets may either express one or both TRAIL-R1 or TRAIL-R2. The invention provides for the use of the TRAIL receptor-binding agents of the invention in cancer therapy.