Cognition is regulated across the 24-h sleep-wake cycle by circadian rhythmicity and sleep homeostasis. To better understand these mechanisms, we used functional neuroimaging (PET, fMRI, EEG/fMRI) both during wakefulness and sleep in normal human volunteers. In a first set of studies, we characterized the neural correlates of cognition during a normal sleep-wake cycle and during sleep-loss. The data show that dynamic changes in brain responses evolve across the sleep-wake and circadian cycles in a regionally-specific manner in such a way that the allocation of cortical resources through subcortical activation is constrained by sleep pressure and circadian phase. In a second set of studies, we show that non rapid eye movement (NREM) sleep is not a state of quiescence but is related with significant regional brain activity in synchrony with slow waves and spindles. A last set of studies aimed at showing that the regional brain activity is modified by previous experience, especially during NREM sleep following spatial learning. These studies provide some insights on the interaction between sleep and waking activity, and their influence on regional brain activity in humans.