The regulation of a variety of cellular processes, such as endocytosis, DNA-repair or signal transduction relies on the inducible modification of proteins with Ubiquitin (Ub). Ub-receptors, i.e., effector proteins carrying Ub-binding domains (UBDs), recognize ubiquitinated proteins and trigger specific cellular responses. The activity of Ub-receptors is controlled by "coupled monoubiquitination" which provides an efficient switch from an active to an inactive conformation. In this chapter we discuss the molecular basis of the underlying processes of coupled monoubiquitination and their physiological significance.