Energy homeostasis is the regulation of energy uptake, storage, and expenditure such that an organism maintains a balanced metabolic state. It requires communication between the so-called metabolic organs, including the central nervous system (CNS), the pancreas, adipose tissue, skeletal muscle, and the liver. For example, nutrients stimulate the pancreas and adipose tissue to secrete hormones such as insulin and leptin, respectively. The hypothalamus in the CNS in turn integrates hormonal and nutrient signals to control energy uptake (appetite), storage, and expenditure. As a nutrient, hormone and energy sensor active in all metabolic organs, mTOR plays a central role in mediating energy homeostasis. Here, we review mTORC1 and mTORC2 in metabolic tissues and their role in the regulation of appetite, glucose homeostasis, and energy balance. The deregulation of mTOR signaling can lead to energy imbalance and metabolic disorders such as obesity and type 2 diabetes.