Adenosine is an inhibitory neuromodulator with tight connection to energy metabolism: extracellular adenosine concentration increases when energy balance in cells turns unfavorable. It has been hypothesized that adenosine is one of the key molecules regulating sleep. Several experiments provide evidence to support this hypothesis. Administration of adenosine or its agonists increase sleep while administration of adenosine antagonists has the opposite effect. Importantly, extracellular adenosine concentration increases is the basal forebrain (BF) during prolonged wakefulness and decreases, when sleep after the wakefulness period is initiated. Blocking the adenosine A1 receptors in the BF during the prolonged wakefulness period will prevent the development of excessive sleep (=recovery sleep), that normally follows prolonged waking, suggesting that, indeed, the increase in adenosine during prolonged wakefulness in one of the key mechanisms of sleep homeostasis. The adenosine response appears to be connected to BF cholinergic cells since specific lesion of these cells abolishes both the increase in extracellular adenosine during prolonged wakefulness and the recovery sleep, introducing further evidence to support adenosine's role as a regulator of sleep homeostasis. An interesting question, that so far remains unanswered, is the origin of adenosine during prolonged wakefulness: is it produced by astrocytes or (cholinergic) neurons?