Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionarily conserved sensor of cellular energy status and has been reported to be involved in chronic inflammatory disorders. AMPK is expressed in immune cells, such as dendritic cells, macrophages, lymphocytes and neutrophils, and is an important regulator of inflammatory responses through the regulation of complex signaling networks in part by inhibiting downstream cascade pathways, such as nuclear factor kB, which is a key regulator of innate immunity and inflammation, as well as acting as a negative regulator of toll-like receptors. Recent data suggest that AMPK dysregulation may participate in neurodegenerative diseases, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and neuropathies. However, there are conflicting reports on the benefits or detrimental effects of AMPK in distinct pathological conditions. This paper offers a review of the recent literature on the pharmacological modulation of the AMPK system as a potential molecular target in the management of neurodegenerative diseases.