It is known since long that energy homeostasis is maintained by multiple mechanisms allowing the brain to sense the nutritional status of the body and adapt behavioral and metabolic responses to changes in fuel availability. In addition, the immune system is also largely dependent on the body’s nutritional status and over the last decade, an abundance of evidence has emerged, demonstrating the close link between metabolism and immunity. Moreover, the brain and the immune system communicate through neurotransmitters, cytokines and endocrine hormones. Therefore nervous, endocrine and immune systems represent a complex network of communication ultimately controlling energy homeostasis. This review is an attempt to summarize these multiple and complex regulatory pathways.