•Dendritic cells (DC) are a diverse subset of immune cells that initiate, orchestrate and regulate anti-tumor immune responses.•Dysregulation of DC activation, licensing and maturation dampens antigen-specific T cell immunity.•Anti-cancer treatments can directly and indirectly modulate DC function.•Therapeutic targeting of DCs may synergize with other immunotherapeutic or anti-cancer treatments to initiate de novo anti-tumor immunity or augment pre-existing responses. Dendritic cells (DC) are key sentinels of the host immune response with an important role in linking innate and adaptive immunity and maintaining tolerance. There is increasing recognition that DC are critical determinants of initiating and sustaining effective T-cell-mediated anti-tumor immune responses. Recent progress in immuno-oncology has led to the evolving insight that the presence and function of DC within the tumor microenvironment (TME) may dictate efficacy of cancer immunotherapies as well as conventional cancer therapies, including immune checkpoint blockade, radiotherapy and chemotherapy. As such, improved understanding of dendritic cell immunobiology specifically focusing on their role in T-cell priming, migration into tissues and TME, and the coordinated in vivo responses of functionally specialized DC subsets will facilitate a better mechanistic understanding of how tumor-immune surveillance can be leveraged to improve patient outcomes and to develop novel DC-targeted therapeutic approaches.