The pineal gland expresses a group of proteins essential for rhythmic melatonin production. This pineal-specific phenotype is the consequence of a temporally and specially controlled program of gene expression. Understanding of pineal circadian biology has been greatly facilitated in recent years by a number of molecular studies, including the cloning of N-acetyltransferase, the determination of the in vivo involvement of the cAMP-inducible early repressor in the regulation of N-acetyltransferase, and the identification of a pineal transcriptional regulatory element and its interaction with the cone-rod homeobox protein. Likewise, appreciation the physiological roles of melatonin has increased dramatically with the cloning and targeted knockout of melatonin receptors. With these molecular tools in hand, we can now address more specific questions about how and why melatonin is made in the pineal at night and about how it influences the rest of the body.