Dendritic cells (DC) are specialized antigen presenting cells that acquire, process, and present tumor-associated antigens to T cells for the induction of antigen-specific tumor immune responses. DC have been shown to infiltrate many tumors but both, circulating and tumor-infiltrating DC from cancer patients, appear to be phenotypically and functionally defective. Several tumor-derived factors such as VEGF, IL-6, IL-10, M-CSF, and STAT-3 have been shown to be responsible for systemic and local DC defects. Furthermore, tumor metabolites such as lactic acid may also critically contribute to DC dysfunction and tumor immune escape. The correction of abnormal DC function might be a requirement for successful vaccine approaches against cancer.