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In mammals, the melatonin-producing pineal gland (PG) receives sympathetic innervation from the superior cervical ganglia (SCG). This chapter describes the role of this innervation on the PG’s ontogeny and rhythmic function, along with consequences to physiology when this regulation is disrupted. The PG and the SCG are components of the circadian timing system (CTS). Therefore, the overall CTS is described, including its oscillatory basis, its synchronization to the light: dark (L:D) cycles, and the dissemination of timing cues to all cells throughout the body. Pineal cellular composition and heterogeneity, cell-cell interactions, and the molecular mechanisms involved in the circadian rhythm of melatonin (MEL), are discussed. The SCG’s bilateral placement among surrounding anatomical landmarks, as well as their afferent and efferent connections, are described and illustrated. In addition, the SCG-related surgical models and the state-of-the art technology used to investigate the connection between SCG and PG are presented. Perspectives and gaps in our understanding are also discussed. We hope this chapter inspires readers to delve deeper into the field of the pineal gland and its main messenger, melatonin, as well as MEL’s impact in health and disease, including as a remedial therapy.

Sympathetic Innervation of the Mammalian Pineal Gland: Its Involvement in Ontogeny and Physiology, and in Pineal Dysfunction