Regulation of sleep and its homeostasis has been modeled from EEG data from many species and formulated as the two process model of sleep regulation. The model shows how factor c, the circadian regulation, is responsible for the timing of sleep and how process s, the homeostatic regulation, is responsible for the duration and intensity of sleep. The model accurately predicts the duration of sleep not only in humans but also in other mammalian species. A lot of research has been dedicated to finding the molecular correlates of sleep homeostasis. The basic concept for a sleep/sleep homeostasis regulating factor has been that it accumulates during waking and is able to induce sleep. Often the increase of the molecule has been related to increased neuronal activity and or/energy depletion during prolonged wakefulness. Several molecules in different parts of the brain show increases during prolonged wakefulness and return to base line levels during recovery sleep, indicating that they may be involved in regulation of sleep homeostasis. Adenosine, nitric oxide (NO), prostaglandins and cytokines are among these molecules and clearly regulate at least some aspects of sleep/sleep homeostasis. Recent research has evidenced that neuronal activity during wakefulness is able to regulate the amount of slow wave sleep during the next sleep period, indicating that not only the duration but also the quality of wakefulness regulates sleep.