Death receptors are a subgroup of TNF-receptor family members that can trigger caspase-8 activation and apoptosis upon interaction with their selective ligands. One of the death receptors, Fas (CD95) and its ligand is critically involved in the regulation of immune homeostasis and effectorfunction. Fas-mediated cell death is a major pathway of cytolytic T-cell-mediated death that is involved in specific killing of tumor cells. Recent investigations summarized herein have shown that defective Fas-signaling due to receptor downregulation or dysfunction, or intracellular inhibition by FLIP (FLICE inhibitory protein) can interfere with Fas-mediated tumor cell death, and thereby favor tumor immune escape.