Since near the time of its discovery over 40 years ago, the serotonergic system has been implicated in the regulation of the sleep-wake cycle. While early studies indicate that serotonin (5-HT) was associated with the initiation and maintenance of sleep, later studies indicate that serotonergic neurons also play a role in inhibiting sleep. As reviewed in this paper, the complex effects of 5-HT in the regulation of sleep is due in part to the fact that 5-HT can act at different areas of the brain that have been associated with the control of sleep and wake. In addition, the recent discovery of multiple 5-HT receptors through the mammalian brain led to the finding that different 5-HT receptors are selectively involved in the regulation of the different sleep states.