Interferon regulatory factors (IRFs) play diverse roles in innate and adaptive immunity. Proteins of this family were originally discovered as key regulators of the interferon (IFN) system, controlling both the induction of IFNs and the response to these cytokines, thereby providing a principal basis for host resistance to pathogens. Subsequent studies have revealed their remarkable functional diversity and shown that, by regulating the development and functions of many different cells of the immune system, IRFs shape the establishment and execution of innate and adaptive responses. Among IRF family proteins, IRF4 exhibits a lymphoid- and myeloid-restricted pattern of expression. It recently proved to represent an essential multifunctional regulator of immune cells, being required for B cell development and terminal differentiation, T helper (Th) cell polarization toward Th2 and Th17, and development of dendritic cells (DCs) of the myeloid lineage. This review deals with the diverse roles of IRF4 in host defense, focusing on its role in development and activation of DC cell subsets, and discusses its potential role in orienting the immune response toward immunity or tolerance.