Functional neuroimaging studies support a role for sleep in restoration/rejuvenation/growth in broad thalamocortical neural networks that play important roles in waking executive function, attention, concentration, working memory, and emotion regulation. This chapter reviews the use of neuroimaging studies that relate to the brain mechanisms of sleepiness. Narcolepsy is a sleep disorder characterized by recurrent daytime sleep attacks and often cataplexy, sleep onset paralysis and hypnagogic hallucinations. The role of functional neuroimaging studies in human narcoleptic patients further clarifies the mechanisms of the extrahypothalamic manifestations of the illness, such as cataplexy, sleep attacks, and hypnogogic hallucinations. Neuroimaging studies related to pharmacotherapy of narcolepsy may reveal insights into the neurobiology of sleepiness. Pharmaceutical agents that produce alertness have been shown to increase activity in arousal networks that maintain generalized thalamocortical activity, reversing sleepiness associated with pathological conditions. Sleepiness therefore appears intimately related to a loss of function in diffuse thalamocortical networks.