The pineal gland acts like a bridge between the nervous and endocrine systems, to serve as the principle regulator of circadian rhythms. The history of pineal research starting with philosophical speculation to its current emergence as a neuroendocrine organ is discussed in this chapter. The chapter also provides an overview of circadian rhythms, their fundamental properties, organization, and the role of the suprachiasmatic nucleus as the master pacemaker. A special emphasis has been made on the genetic and molecular mechanisms underlying circadian oscillations, including core clock genes and transcription–translation feedback loops. Pineal gland anatomy, development, functions, and mechanism of action of its principle hormone have also been discussed. The discovery, biosynthesis, regulation, secretion, and metabolism of melatonin, along with its physiological actions on various systems, are described. Emerging evidence linking circadian disruption and melatonin signaling to metabolic disorders and cancer biology is also discussed. This chapter underscores the pineal gland’s essential role in maintaining temporal homeostasis and coordinating systemic physiology with environmental light–dark cycles.