The pituitary lactogenic hormone prolactin (PRL) exerts various physiological actions in humans and rodents via its binding to a membrane receptor. Beside its role in lactation and reproduction, accumulating evidence suggests that PRL has a crucial impact on energy balance by acting on two key players, the pancreas and the adipose tissue. Adipose tissue is now recognized as an endocrine organ and its metabolic activity appears to play an important role in pathophysiology such as obesity and diabetes. White adipocytes store excess of energy in the form of triglycerides for future need while brown adipocytes metabolize lipids and glucose to produce heat, highlighting their different metabolic functionality. The plasticity of white adipose tissue, by the emergence of beige adipocytes, appears to be essential in energy homeostasis. PRL receptor deficient mice provided direct evidence that PRL signaling is involved in the regulation of adipogenesis affecting energy balance and metabolic adaptation most notably during development. Moreover, it was demonstrated that PRL signaling participates to brown adipose tissue differentiation and function, opening novel understanding of hormonal regulation of energy balance. This review summarizes our current knowledge about PRL signaling and its role on adipose tissue.