The cytotoxic effector functions of NK cells are important for enabling the immune system to cope efficiently with infection and malignancy. Two major mechanisms of cytotoxicity are perforin/granzyme- and death receptor-mediated (e.g., FASL- or TRAIL-mediated) induction of cell death. Many studies, including studies in perforin-deficient animals, have led to the conclusion that perforin/granzyme-mediated induction of cell death is a principal pathway used by NK cells to eliminate virus-infected or transformed cells. However, death receptor-mediated apoptosis may also contribute to NK cell-mediated cytotoxicity, as revealed by more recent reports. In the present paper, we have reviewed current data on death receptor-mediated tumor cell apoptosis by NK cells with a particular emphasis on the role of NK cell FASL in the RMA/RMA-S tumor model.