Dendritic cells (DC) are extremely potent antigen-presenting cells, which can prime both naïve CD4⁺ and CD8⁺ T lymphocytes. In their immature state, DC continuously sample and process antigens from the surrounding environment, but only mature DC express sufficient levels of costimulatory molecules to activate naïve T cells. DC present in tumors are functionally immature owing to the immunosuppressive actions of tumor-derived factors and regulatory T cells, and such immature DC promote immune tolerance to the tumor. Recent studies from animal models suggest that Toll-like receptor (TLR) agonists such as CpG can reverse the tolerogenic state of tumoral DC. Strategies that allow DC to gain access to both tumor antigens and TLR agonists, in situ, can overcome tumor tolerance leading to the induction of potent systemic antitumor immunity.