TNF-related apoptosis-inducing ligand (TRAIL) continues to be intently studied as a cancer therapeutic because of its selective tumoricial activity. We have been interesting in evaluating the ability of TRAIL to induce systemic antitumor immunity through the generation of apoptotic tumor cells. Recent observations suggest that localized administration of TRAIL in combination with CpG ODN generates a systemic antitumor immune response to eliminate the primary tumor and distant metastases.