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The two-process model serves as a major conceptual framework in sleep science. I shall describe how animal experiments aimed at exploring circadian oscillators led to the recognition of a sleep-wake dependent process. Its interaction with a circadian process provided the basis of the two-process model. Simulations could account for the timing and intensity of sleep for a variety of schedules. The model has been extended to incorporate local aspects of sleep and instead of a single circadian pacemaker, multiple peripheral oscillators need to be considered. Presently, the underlying mechanisms are explored at the synaptic level as well as in the domain of the transcriptome and proteome. A close relationship between sleep and metabolism has been recognized. The original interpretation that the emergence of sleep provides an escape from the rigid control imposed by the circadian pacemaker is still upheld.
