Posttranslational modification of proteins by ubiquitinylation is a tightly regulated mechanism which modifies the biochemical and functional properties of target proteins. The ubiquitin tag can therefore be thought of as a “molecular zipcode” which sorts proteins into distinct cellular pathways. Recognition of the ubiquitin moiety is mediated by ubiquitin-binding domains (UBDs) and is believed to involve both structural determinants within the ubiquitin moiety and the target protein itself. Ubiquitin-UBD interactions are critical in regulation of essentially all cellular processes, including apoptosis, antigen processing and immune response pathways, cell cycle progression, endocytosis, protein trafficking, viral infection and gene transcription. As such, ubiquitin-binding domains can be considered as  modular adaptors, which mediate and signal specific recognition of ubiquitin in a variety of biological pathways. Recognition of ubiquitin by UBDs is regulated through diverse mechanisms, including inter- and intra-molecular cooperation, competition and autoinhibition. It is not uncommon to find multiple UBDs in one protein, and a subset of proteins harbour both UBDs and ubiquitin-like domains (UBLs); these so-called “shuttle” proteins are thought to regulate substrate polyubiquitinylation and to deliver substrates to the proteasome. Here we review the functional and structural features of different Ubiquitin-Binding Domains, with particular emphasis on Cks1p, a protein involved in cell cycle control and transcriptional regulation, recently found to interact with ubiquitin in an unconventional fashion, and Rad23p, a shuttle protein whose ability to recognize ubiquitin is regulated by a complex set of intramolecular mechanisms.