The regulation of systemic energy balance is a complex process that is tightly controlled by the cross-talk of central and peripheral endocrine signals and that depends on constant signal integration. Key peripheral organs implicated in this process are the brain, the adipose tissue, and the gastrointestinal (GI) tract with its adjacent digestive organs, the pancreas and the liver. The aim of this chapter is to discuss how endocrine signals released or received by these organs affect our sensation of hunger and satiety to modulate energy intake and expenditure. Complementing Chapter 3 (Appetite regulation), a special focus is given on peripheral tissues like the adipose tissue and the GI tract as the largest endocrine organ of the body.