The purpose of this contribution is to review our current understanding of the source and biochemistry of the circadian efferent input to the eyes of the American horseshoe crab Limulus polyphemus and the impact of this input on the structure, physiology and biochemistry of Limulus eyes. Special emphasis is given to the role of the biogenic amine octopamine and biochemical cascades it activates in the eyes. In addition to reviewing published data, we present new data showing that octopamine elevates cAMP levels in Limulus lateral eyes, and we partially characterize the pharmacology of the receptors involved in this response. We also present new data showing that octopamine regulates gene expression in Limulus lateral eyes by activating a cAMP cascade.