Tumor necrosis factor (TNF) is a cytokine that mediates tumor necrosis. To date, 20 different members of the TNF super-family and 21 different receptors have been identified. All ligands of the TNF super-family have been found to activate transcription factor NF-κB and c-Jun kinase. Members of this family have diverse biological effects, including induction of apoptosis, promotion of cell survival, and regulation of the immune system and hematopoiesis. The current review focuses on the biological effects of TNF-related apoptosis-inducing ligand (TRAIL), a TNF super-family member which, a few years ago, generated considerable enthusiasm for its anticancer activity, not accompanied by general toxicity in most normal tissues and organs. © 2004 Wiley-Liss, Inc.