Energy homeostasis in the body is maintained by regulating the nutrient intake, energy storage, and energy utilization. This is brought about by the interplay of endocrine, neural, and metabolic pathways. This chapter provides a comprehensive overview of the role of endocrine system in the control of metabolism. Emphasis has been made on the integration of central and peripheral signals governing energy balance in both physiological and pathological states. The hypothalamus functions as a central hub, integrating neurohormonal signals mainly from the gastrointestinal tract, pancreas, liver, and adipose tissue, translating these signals into appropriate endocrine and autonomic response. Adipose tissue, once considered to be a passive energy depot, is now recognized as an active endocrine organ. This chapter reviews the role of hormones insulin, glucagon, incretins, ghrelin, thyroid hormones, glucocorticoids, and catecholamines in orchestrating anabolic and catabolic states. A particular emphasis has been made on metabolism of lipids, carbohydrates, and proteins by the hormones. Pathophysiological correlates, such as obesity and type 1 and type 2 diabetes mellitus, have also been discussed linking them with lipostat and various programming hypotheses. This chapter highlights the central role of hormonal regulation in maintaining energy homeostasis by integrating various molecular, physiological, and clinical perspectives.