This paper presents an overview on the epithalamus of vertebrates, with particular reference to the pineal and to the asymmetrical organization of the habenular nuclei in lower vertebrates. The relationship between the pineal and the habenulae in the course of phylogenesis is here emphasized, taking data in the frog as example. Altogether the data support the hypothesis, put forward also in earlier studies, of a correlation of habenular asymmetry in lower vertebrates with phylogenetic modification of the pineal complex. The present re-visitation was also stimulated by recent data on the asymmetrical expression of Nodal genes, which involves the pineal and habenular structures in zebrafish. The comparative analysis of data, from cyclostomes to mammals, suggests that transformation of epithalamic structures may play an important role in brain evolution. In addition, in mammals, including rodents, a remarkable complexity has evolved in the organization of the habenulae and their functional interactions with the pineal gland. The evolution of these two epithalamic structures seems to open also new perspectives of knowledge on their implication in the regulation of biological rhythms.