One of the key features of sleep is that if the duration of a waking period is prolonged, the following sleep period will be longer, including more slow-wave activity. This homeostasis is explained by production of sleep pressure that accumulates during the waking period. It is generally accepted that neuronal activity, in one way or other, is the driving force for accumulation of sleep pressure, both during spontaneous sleep-wake cycle and during prolonged wakefulness. Prolonged wakefulness is associated with increased energy consumption, production of danger signals and modulations in neural plasticity. Data derived from experiments with Drosophila melanogaster introduces a fascinating window to the basic mechanisms of sleep and sleep homeostasis, and undoubtedly sheds light to the mechanisms of sleep regulation also in humans. However, the existence of substantial cortex, which is regarded as a key actor in mammalian NREM sleep regulation, will add to the complexity of the regulatory circuits.