Glycogen synthase kinase-3β (GSK3β), primarily described as a regulator of glycogen metabolism, is a molecular hub linking numerous signaling pathways and regulates many cellular processes like cytoskeletal rearrangement, cell migration, apoptosis, and proliferation. In neurons, the kinase is engaged in molecular events related to the strengthening and weakening of synapses, which is a subcellular manifestation of neuroplasticity. Dysregulation of GSK3β activity has been reported in many neuropsychiatric conditions, like schizophrenia, major depressive disorder, bipolar disorder, and Alzheimer’s disease. In this review, we describe the kinase action in reward circuit-related structures in health and disease. The effect of pharmaceuticals used in the treatment of addiction in the context of GSK3β activity is also discussed.