Glycogen synthase kinase 3β (GSK3β), a multifunctional serine/threonine kinase found in all eukaryotes, had been initially identified as a key regulator of insulin-dependent glycogen synthesis. It is now known that GSK3β functions in diverse cellular processes including proliferation, differentiation, motility and survival. Aberrant regulation of GSK3β has been implicated in a range of human pathologies including non-insulin-dependent diabetes mellitus, cardiovascular disease, some neurodegenerative diseases, and bipolar disorder. As a consequence, the therapeutic potential of GSK3β inhibitors has become an important area of investigation. However, GSK3β also participates in neoplastic transformation and tumor development. The role of GSK3β in tumorigenesis and cancer progression remains controversial; it may function as a “tumor suppressor” for certain types of tumors, but promotes growth and development for some others. GSK3β also mediates drug sensitivity/resistance in cancer chemotherapy. Therefore, although GSK3β is an attractive therapeutic target for a number of human diseases, its potential impact on tumorigenesis and cancer chemotherapy needs to be carefully evaluated. This mini-review discusses the role of GSK3β in tumorigenesis/cancer progression as well as its modulation of cancer chemotherapy.