AMPK is a conserved serine/threonine kinase that maintains cellular energy homeostasis. It is regulated by various mechanisms, including allosteric regulation and post-translational modifications. AMPK plays a critical role in metabolic and physiological processes and is dysregulated in diseases such as obesity, diabetes, and cancer. AMPK is a promising target for the prevention and treatment of these diseases. The regulation of AMPK involves multiple pathways, including phosphorylation at T172 of the α-subunit, calcium signaling, and interactions with other proteins. AMPK also regulates lipid and glucose metabolism, protein synthesis, autophagy, and mitochondrial biogenesis. It is involved in the regulation of inflammation and redox balance, which are critical in disease pathogenesis. AMPK activation has been shown to improve insulin sensitivity and reduce inflammation, which are key factors in the prevention and treatment of diabetes and cancer. However, AMPK can also promote cancer progression by enabling metabolic adaptation of tumor cells. The role of AMPK in cancer is complex and depends on the stage of carcinogenesis. AMPK activation is beneficial for preventing diabetes and cancer, while AMPK inhibition may be useful for treating established cancers. Two old drugs, aspirin and metformin, have been shown to activate AMPK and exert anti-inflammatory effects, which may be key mechanisms in their therapeutic benefits. Overall, AMPK is a promising target for the prevention and treatment of metabolic and chronic diseases.AMPK is a conserved serine/threonine kinase that maintains cellular energy homeostasis. It is regulated by various mechanisms, including allosteric regulation and post-translational modifications. AMPK plays a critical role in metabolic and physiological processes and is dysregulated in diseases such as obesity, diabetes, and cancer. AMPK is a promising target for the prevention and treatment of these diseases. The regulation of AMPK involves multiple pathways, including phosphorylation at T172 of the α-subunit, calcium signaling, and interactions with other proteins. AMPK also regulates lipid and glucose metabolism, protein synthesis, autophagy, and mitochondrial biogenesis. It is involved in the regulation of inflammation and redox balance, which are critical in disease pathogenesis. AMPK activation has been shown to improve insulin sensitivity and reduce inflammation, which are key factors in the prevention and treatment of diabetes and cancer. However, AMPK can also promote cancer progression by enabling metabolic adaptation of tumor cells. The role of AMPK in cancer is complex and depends on the stage of carcinogenesis. AMPK activation is beneficial for preventing diabetes and cancer, while AMPK inhibition may be useful for treating established cancers. Two old drugs, aspirin and metformin, have been shown to activate AMPK and exert anti-inflammatory effects, which may be key mechanisms in their therapeutic benefits. Overall, AMPK is a promising target for the prevention and treatment of metabolic and chronic diseases.