Glycogen synthase kinase-3 (GSK-3) was originally identified and purified in the late 1970s as a kinase (serine/threonine kinase) capable of phosphorylating and inactivating the enzyme glycogen synthase. GSK-3 is now known to occur in two isoforms: GSK- 3α and GSK-3β. Their amino acid sequences show 84% identity overall, and 98% identity within their catalytic domain. Beyond its role in glycogen metabolism, GSK-3 has been found to play pivotal roles in a diverse range of cellular functions, including cell proliferation, cell differentiation, apoptosis, and the Wnt signaling cascade. The pathways in which GSK-3 acts as a key regulator have been implicated in the development of a wide range of diseases, including Alzheimers disease, other neurodegenerative diseases, diabetes, bipolar affective disorder, and cancer. Moreover, recent findings have shown that GSK-3 is involved in the pathophysiology of alopecia, schizophrenia, and circadian rhythm disorders. Because of the discovery of the diverse roles of GSK-3 in the development of the above diseases, the pharmaceutical industry has recently made enormous efforts to synthesize selective and potent inhibitors of GSK-3. Several potent inhibitors have already been synthesized, and their pharmacological effects in both in vitro cell-based assays and in several animal models have confirmed important pathophysiological roles of GSK-3 and the therapeutic potential of GSK-3 inhibitors. This article reviews the molecular and pharmacological properties of GSK-3, and discusses its involvement in the pathophysiology of various diseases. It also includes a discussion of recent progress in the development of GSK-3 inhibitors, and their relevance as therapeutic agents for the treatment of diseases in which GSK dysfunctions may be involved.