Chemokines have fundamental roles in regulating immune and inflammatory responses, primarily through their control of leukocyte migration and localization. The biological functions of chemokines are typically mediated by signalling through G protein-coupled chemokine receptors, but chemokines are also bound by a small family of atypical chemokine receptors (ACKRs), the members of which are unified by their inability to initiate classical signalling pathways after ligand binding. These ACKRs are emerging as crucial regulatory components of chemokine networks in a wide range of developmental, physiological and pathological contexts. In this Review, we discuss the biochemical and immunological properties of ACKRs and the potential unifying themes in this family, and we highlight recent studies that identify novel roles for these molecules in development, homeostasis, inflammatory disease, infection and cancer.