Nowadays non-alcoholic fatty liver disease (NAFLD) is thought to be a multisystemic disease, characterized by different extrahepatic manifestations, including but not limited to the cardiovascular diseases, obesity, type 2 diabetes mellites, osteoporosis, and depression. The high association of NAFLD with such a variety of diseases of other organs may be attributed to the well-known pathophysiological mechanisms, namely, insulin resistance, chronic inflammation, and vitamin D deficiency. Recently published data also suggest the role of skeletal muscles in the development of NAFLD and extrahepatic manifestations, which may be explained at least in part by their participation in lipid and glucose metabolism. In this chapter we will discuss the interconnection between the NAFLD, decreased muscle strength and mass (i.e., sarcopenia), and depression. These three seemingly unrelated conditions actually may negatively impact on the course of each other and alter patient adherence to the recommendations on lifestyle modification and treatment.