Human sleep is considered a global phenomenon, orchestrated by central specialized neuronal networks modulating the whole-brain activity. However, recent studies point to a local regulation of sleep. Sleep disorders, such as sleepwalking, suggest that electroencephalographic (EEG) features of sleep and wakefulness might be simultaneously present in different cerebral regions. Recently, intracranial EEG recording techniques, mainly applied for the presurgical evaluation of drug-resistant epileptic patients, have provided new and interesting information on the activity of different cortical and subcortical structures during sleep in humans. In particular, it has been observed that the thalamus, during the transition between wake and sleep undergoes a deactivation process that precedes the one occurring within the cortex, with extensive cortical territories maintaining an activated pattern for several minutes after the thalamic deactivation. Very recent intracerebral EEG studies have also shown that human NREM sleep can be characterized by the coexistence of wake-like and sleep-like EEG patterns in different cortical areas. Moreover, unit-firing recordings in multiple brain regions of neurosurgical patients evidenced that most sleep slow waves and the underlying active and inactive neuronal states do occur locally. These findings add a new dimension to the concept of local sleep regulation and opens new perspectives in the interpretation of the substrates underlying behavioral states of vigilance. The implications for sleep medicine are also discussed.