The article reviews the Apo2 ligand (Apo2L/TRAIL) and its interaction with death receptors (DRs) and decoy receptors (DcRs). Apo2L/TRAIL is a member of the tumor necrosis factor (TNF) gene superfamily that induces apoptosis in transformed cells but not in normal cells. The receptor system for Apo2L/TRAIL consists of two DRs (DR4 and DR5) and three DcRs (DcR1 and DcR2). The article discusses the biochemical pathways involved in Apo2L/TRAIL-induced apoptosis, including the formation of the death-inducing signaling complex (DISC) and the activation of caspases. It also explores the role of the Bcl-2 family in apoptosis induction and the influence of other signaling pathways such as NF-κB, p53, and kinase signaling. The article highlights the therapeutic potential of Apo2L/TRAIL in cancer treatment, noting its effectiveness in inducing apoptosis in various cancer cell lines and its potential to synergize with chemotherapy and radiotherapy. However, it emphasizes the need for further preclinical safety testing to address concerns about hepatotoxicity. Finally, the article discusses the physiological role of Apo2L/TRAIL in immune surveillance and its potential to prevent autoimmune diseases.The article reviews the Apo2 ligand (Apo2L/TRAIL) and its interaction with death receptors (DRs) and decoy receptors (DcRs). Apo2L/TRAIL is a member of the tumor necrosis factor (TNF) gene superfamily that induces apoptosis in transformed cells but not in normal cells. The receptor system for Apo2L/TRAIL consists of two DRs (DR4 and DR5) and three DcRs (DcR1 and DcR2). The article discusses the biochemical pathways involved in Apo2L/TRAIL-induced apoptosis, including the formation of the death-inducing signaling complex (DISC) and the activation of caspases. It also explores the role of the Bcl-2 family in apoptosis induction and the influence of other signaling pathways such as NF-κB, p53, and kinase signaling. The article highlights the therapeutic potential of Apo2L/TRAIL in cancer treatment, noting its effectiveness in inducing apoptosis in various cancer cell lines and its potential to synergize with chemotherapy and radiotherapy. However, it emphasizes the need for further preclinical safety testing to address concerns about hepatotoxicity. Finally, the article discusses the physiological role of Apo2L/TRAIL in immune surveillance and its potential to prevent autoimmune diseases.