Dendritic cells (DCs) play a crucial role in linking innate and adaptive immunity, by virtue of their unique ability to take up and process antigens in the peripheral blood and tissues and, upon migration to draining lymph nodes, to present antigen to resting lymphocytes. Notably, these DC functions are modulated by cytokines and chemokines controlling the activation and maturation of these cells, thus shaping the response towards either immunity or tolerance.An ensemble of recent studies have emphasized an important role of type I IFNs in the DC differentiation/activation, suggesting the existence of a natural alliance between these cytokines and DCs in linking innate and adaptive immunity. Herein, we will review how type I IFNs can promote the ex vivo differentiation of human DCs and orient DC functions towards the priming and expansion of protective antitumor immune responses. We will also discuss how the knowledge on type I IFN-DC interactions could be exploited for the design of more selective and effective strategies of cancer immunotherapy.