Although there is significant progress with respect to the delineation of the neurobiology of sleep and wakefulness, the circadian aspects of sleep, the nonrapid eye movement-rapid eye movement (NREM-REM) oscillation, and sleep-related phasic events, substantially less is known about the neurobiological abnormalities that give rise to sleep disorders in general and insomnia in particular. This chapter reviews the issues that pertain to the definition of insomnia, with special consideration to how the definition of insomnia may influence the attempt to define the neurobiological aspects of the disorder. It also reviews the regulation of sleep and wakefulness and provides a framework for the consideration of insomnia as a disorder that not only has multiple determinants but also can be described in terms of multiple parallel processes. The lack of diagnostic specificity, in turn, is expected to substantially complicate the search for, and identification of, the neuronal systems that, when functioning abnormally, produce these different outcomes. The illness state, therefore, is thought to be rooted in the dysregulation of the neuronal systems related to sleep initiation or maintenance.