Monocyte/macrophages play an important role in orchestrating the immune response. The present review refers to C/EBPβ, which is a key transcription factor regulating monocytic gene expression. Following a general introduction to C/EBPβ, this article focuses on activators and regulators of the C/EBPβ system in monocytic cells, including differentiating agents, cytokines, and bacterial products as well as associated signaling pathways. Furthermore, C/EBPβ target genes in monocytic cells are summarized and resulting functions are described, including regulation of proliferation and differentiation as well as orchestration of processes of mainly the innate immune response. In addition, a variety of disease stages are described in which a dysregulation of the C/EBPβ system may be involved. A detailed knowledge of the C/EBPβ system in monocytic cells may help to further understand the difference between inflammatory and malignant proliferation as well as additional regulatory facets of innate immunity.