TRAIL (tumor necrosis factor related apoptosis inducing ligand) is a cytokine proposed to be used in cancer therapy, since it kills cancer cells but not normal cells. Also, recent studies report that TRAIL inhibits the development of arthritis. In order to investigate the role of TRAIL in health and disease, monoclonal antibodies against TRAIL have been developed. This chapter gives an overview of different monoclonal antibodies against TRAIL which are published or commercially available. Monoclonal antibodies against TRAIL are useful in different immunological techniques, and this chapter presents an overview of the applications of these antibodies with a focus on immunoassays for detection of soluble TRAIL. In addition, the physiological significance of some results obtained by using monoclonal antibodies against TRAIL are discussed.