The Y-box-binding protein (YB-1) represents the most evolutionary conserved nucleic-acid-binding protein currently known. YB-1 is a member of the cold-shock domain (CSD) protein superfamily. It performs a wide variety of cellular functions, including transcriptional regulation, translational regulation, DNA repair, drug resistance and stress responses to extracellular signals. As a result, YB-1 expression is closely associated with cell proliferation. In this review, we will begin by briefly describing the characteristics of YB-1 and will then summarize the pleiotropic functions brought about via DNA–RNA transaction and protein–protein interactions. In addition, we will discuss the diverse range of potential physiological and pathological functions of YB-1. BioEssays 25:691–698, 2003. © 2003 Wiley Periodicals, Inc.