Primary insomnia is defined as difficulties in falling asleep, maintaining sleep or non-restorative sleep accompanied by significantly impaired daytime functioning in the absence of a specific physical, mental or substance-related cause. The current review provides substantial support for the concept that hyperarousal processes from the molecular to the higher system level play a key role in the pathophysiology of primary insomnia. Autonomous, neuroendocrine, neuroimmunological, electrophysiological and neuroimaging studies demonstrate increased levels of arousal in primary insomnia during both night and daytime. In the light of neurobiological theories of sleep–wake regulation, primary insomnia may be conceptualized as a final common pathway resulting from the interplay between a genetic vulnerability for an imbalance between arousing and sleep-inducing brain activity, psychosocial/medical stressors and perpetuating mechanisms including dysfunctional sleep-related behavior, learned sleep preventing associations and other cognitive factors like tendency to worry/ruminate.