B lymphocyte-induced maturation protein-1 (Blimp-1), the transcription factor encoded by the gene Prdm1, plays a number of crucial roles in the adaptive immune system, which result in the maintenance of key effector functions of Band T-cells. Emerging clinical data, as well as mechanistic evidence from mouse studies, have additionally identified critical functions of Blimp-1 in the maintenance of immune homeostasis by the mononuclear phagocyte (MNP) system. Blimp-1 regulation of gene expression affects various aspects of MNP biology, including developmental programmes such as fate decisions of monocytes entering peripheral tissue, and functional programmes such as activation, antigen presentation and secretion of soluble inflammatory mediators. The highly tissue-, subset-and state-specific regulation of Blimp-1 expression in MNPs suggests that Blimp-1 is a dynamic regulator of immune activation, integrating environmental cues to fine-tune the function of innate cells. In this review, we will discuss the current knowledge regarding Blimp-1 regulation and function in macrophages and dendritic cells.