The hypothalamus controls the release of hormones by the pituitary and is involved in control of food and water intake, sexual behavior, reproduction and daily cycles in physiological state and behavior, temperature regulation and emotional responses. Adenosine-5'-triphosphate (ATP) and its metabolic products contribute to these functions, acting as agonists for adenosine and P2Y receptors and two-transmembrane domain P2X receptor channels. This review summarizes the recent findings on purinergic receptor expression and their roles in signaling and cellular function in secretory and supporting cells of the hypothalamopituitary system. ATP secretion by these tissues, the enzymes involved in ATP hydrolysis, and the relevance of this pathway for sequential activation of receptors and termination of signaling are also discussed.