Statins are a group of lipid-lowering drugs that inhibit cholesterol biosynthesis and have anti-inflammatory, anti-tumor, and immunomodulatory properties. Several lines of evidence indicate that statins regulate multiple proteins associated with the regulation of differing cellular pathways. The 5'-adenosine monophosphate-activated protein kinase (AMPK) pathway plays an important role in metabolism homeostasis with effects on cellular processes including apoptosis and the inflammatory responses through several pathways. Recently, it has been shown that statins can affect the AMPK pathway in differing physiological and pathological ways, resulting in anti-cancer, cardio-protective, neuro-protective, and anti-tubercular effects; additionally, they have therapeutic effects on non-alcoholic fatty liver disease and diabetes mellitus-associated complications. Statins activate AMPK as an energy sensor that inhibits cell proliferation and induces apoptosis in cancer cells, whilst exerting its cardio-protective effects through inhibition of inflammation and fibrosis, and promotion of angiogenesis. Furthermore, statin-associated AMPK activation leads to decreased lipid accumulation and decreased amyloid beta deposition in the liver and brain, respectively, and may have therapeutic effects on the liver and neurons. In this review, we summarize the results of studies of AMPK-associated therapeutic effects of statins in different pathological conditions.