Immune responses are regulated by effector cytokines and chemokines that signal through cell surface receptors. Mammalian decoy receptors - which are typically soluble or inactive versions of cell surface receptors or soluble protein modules termed binding proteins - modulate and antagonize signalling by canonical effector-receptor complexes. Viruses have developed a diverse array of molecular decoys to evade host immune responses; these include viral homologues of host cytokines, chemokines and chemokine receptors; variants of host receptors with new functions; and novel decoy receptors that do not have host counterparts. Over the past decade, the number of known mammalian and viral decoy receptors has increased considerably, yet a comprehensive curation of the corresponding structure-mechanism relationships has not been carried out. In this Review, we provide a comprehensive resource on this topic with a view to better understanding the roles and evolutionary relationships of mammalian and viral decoy receptors, and the opportunities for leveraging their therapeutic potential.