Treatment of cancer with means other than chemo- and radiation therapy becomes more and more important. Through the better understanding of tumor biology approaches towards the cure of cancer interfering with the pathophysiological mechanisms of malignancy can be considered. Hodgkin's disease is a good example for the role of the immune system in cancer. The Reed-Sternberg (RS) cells, malignant cells of Hodgkin's disease (HD), are surrounded by tumor infiltrating lymphocytes (TILs) and still evade immunesurveillance. In this respect the importance of the superfamily of tumor necrosis factor (TNF) receptors and ligands is becoming more and more clear. Ligand-receptor interaction either leads to death or survival signals. Many of these receptors and ligands are expressed by the RS cells and the surrounding lymphocytes. Their expression and function in HD are discussed and future directions for possible therapeutical investigations are proposed.