The biennial TNF-family conferences have been held over the past 20 years, from the time that TNF was cloned. These meetings have followed the enormous progress in this field. Much is now known about the members of the TNF ligand and receptor families, their signaling proteins, mechanisms of action and cellular functions. This volume is the proceedings of the 12th TNF International Conference, held in April 2009. This conference focuses on the physiological, pathophysiological, and medical significance of these important regulators. Sessions at the meeting specifically address their involvement in immunity, development, apoptosis, autoimmunity, cancer, and infection, the normal function and pathology of the neuronal system, as well as major unresolved questions about their mechanisms of action.