The serotonin and circadian systems are principal regulatory networks of the brain. Each consists of a unique set of neurons that make widespread neural connections and a defined gene network of transcriptional regulators and signaling genes that subserve serotonergic and circadian function at the genetic level. These master regulatory networks of the brain are extensively intertwined, with reciprocal circuit connections, expression of key genetic elements for serotonin signaling in clock neurons and expression of key clock genes in serotonergic neurons. The reciprocal connections of the serotonin and circadian systems likely have importance for neurobehavioral disorders, as suggested by their convergent contribution to a similar range of mood disorders including seasonal affective disorder (SAD), bipolar disorder, and major depression, and as suggested by their overlapping relationship with the developmental disorder, autism spectrum disorder. Here we review the neuroanatomical and genetic basis for serotonin-circadian interactions in the brain, their potential relationship with neurobehavioral disorders, and recent work examining the effects on the circadian system of genetic perturbation of the serotonergic system as well as the molecular and behavioral effects of developmental imprinting of the circadian system with perinatal seasonal light cycles. (C) 2011 Published by Elsevier Ltd on behalf of IBRO.