Therapeutic immunization leading to cancer regression remains a significant challenge. Successful immunization requires activation of adaptive immunity, including tumor specific CD4 T cells and CD8 T cells. Generally, the activation of T cells is compromised in patients with cancer because of immune suppression, loss of tumor antigen expression, and dysfunction of antigen-presenting cells. Antigen-presenting cells such as dendritic cells (DCs) are key for the induction of adaptive antitumor immune responses. Recently, attention has focused on novel adjuvants that enhance dendritic cell function and their ability to prime T cells. Agonists that target toll-like receptors are being used clinically either alone or in combination with tumor antigens and showing initial success both in terms of enhancing immune responses and eliciting antitumor activity. This review summarizes the application of these adjuvants to treat cancer and the potential for boosting responses in vivo.