AMP-activated protein kinase (AMPK) constitutes a molecular hub for cellular metabolic control, common to all eukaryotic cells. Numerous reports have established how AMPK responds to changes in the AMP:ATP ratio as a measure of cellular energy levels. In this way, it integrates control over a number of metabolic enzymes and adapts cellular processes to the current energy status in various cell types, such as muscle and liver cells. The role of AMPK in the development, function, and maintenance of the nervous system, on the other hand, has only recently gained attention. Neurons, while highly metabolically active, have poor capacity for nutrient storage and are thus sensitive to energy fluctuations. Recent reports demonstrate that AMPK may have neuroprotective properties and is activated in neurons by resveratrol but also by metabolic stress in the form of ischemia/hypoxia and glucose deprivation. Novel studies on AMPK also implicate neuronal activity as a critical factor in neurodegeneration. Here we discuss the latest advances in the knowledge of AMPK's role in the metabolic control and survival of excitable cells.