Besides tagging proteins for degradation, ubiquitin is now recognized as a signaling module for diverse cellular processes, including progression through the cell cycle, DNA repair, gene transcription, receptor trafficking and endocytosis. Recent advances have indicated the existence of a wide variety of ubiquitin-binding proteins that, upon recognition of conjugated ubiquitin moieties, can control assembly of complex signaling networks. Small ubiquitin-like proteins, like SUMO, emerge to play biological roles distinct from ubiquitin, and require specific recognition by a dedicated set of proteins. Identification and characterization of recognition motifs and domains for ubiquitin-like proteins have just begun, promising new insights into the diversity of functions ubiquitin family proteins have in physiological and pathological settings.