One of the most notable developments in research concerning Alzheimer's disease is the solid evidence directly linking glycogen synthase kinase-3 (GSK-3) to most, if not all, of the major mechanisms known to contribute to the neuropathology of the disease. GSK-3 interacts with multiple components of the plaque-producing amyloid system associated with Alzheimer's disease. GSK-3 participates in phosphorylating the microtubule-binding protein tau, which may contribute to the formation of neurofibrillary tangles in Alzheimer's disease. GSK-3 interacts with presenilin and other Alzheimer's disease-associated proteins. GSK-3 has a central role in neuronal plasticity and memory. GSK-3 promotes both inflammation and apoptosis. These many links between GSK-3 and Alzheimer's disease are discussed in this chapter.