Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are neurodegenerative disorders that are characterized by a progressive degeneration of nerve cells eventually leading to dementia. While these diseases affect different neuronal populations and present distinct clinical features, they share in common several features and signaling pathways. In particular, energy metabolism defects, oxidative stress, and excitotoxicity are commonly described and might be correlated with AMP-activated protein kinase (AMPK) deregulation. AMPK is a master energy sensor which was reported to be overactivated in the brain of patients affected by these neurodegenerative disorders. While the exact role played by AMPK in these diseases remains to be clearly established, several studies reported the implication of AMPK in various signaling pathways that are involved in these diseases' progression. In this chapter, we review the current literature regarding the involvement of AMPK in the development of these diseases and discuss the common pathways involved.