Over the last decades, the negative health consequences of obesity have triggered massive searches for the cause of - and potential solutions for - the excessive mismatch between calorie consumption and expenditure. The concepts of malfunctioning hypothalamic neurotransmission and impaired related neuromodulatory networks in other brain regions have attracted considerable attention as they may partially explain metabolic abnormalities. While numerous and important efforts are underway to scientifically dissect the neuronal signaling pathways involved in metabolic sensing and regulation, the roles of astroglial cells represent a relatively understudied area. This gap in knowledge is particularly evident in the neuroendocrine control of glucose and lipid metabolism. This review presents evidence that in regard to metabolism, astrocytes act not only as an energy supplier for neurons, but may also play key roles in metabolic sensing by expressing metabolic related receptors and regulators. Moreover, the astrocytosis observed during calorie-rich high-fat diet indicates that astrocytes could be involved in developing metabolic abnormalities. Finally, potential obstacles and pitfalls for studying the role of astrocytes in metabolic sensing and regulation are discussed. Copyright © 2011 S. Karger AG.