This chapter reviews brain imaging studies that comment on whether or not there is abnormal brain function in insomnia patients that may in some way relate to their difficulty in sleeping. It provides a systems neuroscience view of a hierarchical arousal network in the central nervous system. Human sleep neuroimaging studies in healthy subjects support the involvement of these basic arousal networks in non-rapid eye movement (NREM) sleep. Blood flow has been shown to correlate negatively with the presence of NREM sleep in the pontine reticular formation, and in the basal forebrain/hypothalamus. Pharmacotherapy for insomnia may have some of its mechanism of action on the limbic and paralimbic structures, especially the antidepressant medications. Traditional sedative-hypnotic approaches appear to target brainstem and hypothalamic arousal networks in insomnia patients while behavioral treatments and frontal cerebral hypothermia appear to target frontal hyperarousal in insomnia patients.