Sleep and pain are both vital functions on which wellbeing, health, and life itself depend. These two complex states interact in several ways serving homeostasis, but they are also regulated by a well-orchestrated, multi-oscillatory mechanism characterizing the Circadian Timing System. This interaction, which benefits critical physiological challenges, is also clinically crucial, as it mutually affects sleep and pain-related disturbances. It impacts pathophysiological pathways and relevant clinical aspects of many disorders. Furthermore, therapeutic success is frequently dependent on the adequate management of this cycle. The relationship of sleep and pain is undoubtedly of major relevance for diagnosis and successful management of various health conditions and disorders.