In spite of recent advances in cancer therapy, some tumors still remain incurable and novel therapeutic approaches need to be developed. Apoptosis is a cell death inducing mechanism and is actually one of the most obvious targets for cancer treatment. It becomes clear that this regulation is more complex than previously expected, and multiple signalling pathways for cell death have to be considered. Agents with the property of inducing tumor cell death, such as TNF/TNFR superfamily members, also called "death receptors", represent an attractive therapeutic approach. Our team identified another member of this family, HVEM and its ligand LIGHT, as promising therapeutic targets. HVEM was known as a costimulatory molecule, but this role is getting more complex with the identification of new ligands and the highlights of new functions. So, HVEM could combine a pro-apoptotic effect with the immune system activation. This review will first focus on mechanisms and new insights in therapeutic application of TNF receptors. Then we will present new functions for LIGHT and HVEM and how these functions may provide new opportunities for antitumoral therapy and more effective treatments.