Life or death of a cancer cell is influenced by autocrine/paracrine and immune/nonimmune interactions that ultimately result in the victory of either the host or the cancer cell. Cross-linking of the soluble or membrane-bound Fas ligand (FasL/CD95L) with its receptor (Fas/CD95) induces apoptosis of Fas-expressing cells. This apoptotic pathway has been utilized by cancer cells as a mechanism of immune escape toward the activated lymphocytes of the host. However, in some systems, this down-regulating mechanism may be directed against the cancer cell either by self-attack or by neighboring immune defense cells. Soluble FasL may contribute to the process in either direction. Additionally, nonimmune Fas/FasL interactions also appear to have important contributions to cancer development, invasion, and therapy by allowing survival of cells with unrepaired damaged DNA (when defective); by degrading neighboring tissues; and by inducing chemo/radiotherapy resistance. Thus, the expression of FasL by malignant cell has several implications in cancer biology and underscores similarities between the cancer cell and the trophoblast that also expresses FasL and displays invasion characteristics.