Astrocytes are most abundant glial cells in the central nervous system that reside between the microvascular network of the brain and neuronal synapses, thus mediating the absorption of nutrients from the systemic circulation. In addition, due to their unique anatomical location, astrocytes have a high enzymatic capacity for glycolysis, glycogenesis and lipid metabolism. This makes it possible to provide neurons with necessary nutrients as a source of energy, indicating a pivotal role of astrocytes in brain metabolism. Therefore, dysfunction of astroglia can lead to the development of neurodegenerative diseases in which metabolic disturbances speed up neuronal damage. Given the important role of astrocytes in the regulation of brain homeostasis and their close metabolic relationship with neurons, we address here the plasticity of astrocyte energy metabolism in physiological conditions and its effect on brain functions during the development of neurodegenerative diseases. A deeper insight into the mechanism underlying astrocyte metabolic plasticity will help identify novel potential diagnostic biomarkers and therapeutic targets to correct neurodegeneration and age-related brain dysfunctions.