Ubiquitin acts as a versatile cellular signal that controls a wide range of biological processes including protein degradation, DNA repair, endocytosis, autophagy, transcription, immunity, and inflammation. The specificity of ubiquitin signaling is achieved by alternative conjugation signals (monoubiquitin and ubiquitin chains) and interactions with ubiquitin-binding proteins (known as ubiquitin receptors) that decode ubiquitinated target signals into biochemical cascades in the cell. Herein, we review the current knowledge pertaining to the structural and functional features of ubiquitin-binding proteins and the mechanisms by which they recognize various types of ubiquitin topologies. The combinatorial use of diverse ubiquitin-binding domains (UBDs) in full-length proteins, selective recognition of chains with distinct linkages and length, and posttranslational modifications of ubiquitin receptors or multivalent interactions within protein complexes illustrate a few mechanisms by which a circuitry of signaling networks can be rewired by ubiquitin-binding proteins to control cellular functions in vivo.