In addition to these non-functional receptors, or the lack of expression of the agonistic receptors DR4 or DR5 [37,38,39], resistance to TRAIL-induced cell death can arise in tumor cells owing to a large variety of events, including a loss of caspase-8 expression [40] or the overexpression of c-FLIP [41,42] (Figure 2), the main inhibitor of caspase-8 [43]. This evidence concerns the gene CFLAR and neoplasm.