Nucleotides and dinucleotides have interesting physiological actions in the eye. The involvement of these naturally occurring substances in processes such as tear secretion, intraocular pressure, corneal wound healing, or retinal detachment is discussed. Nucleotides are present in rabbit and human tears and they exert interesting effects, such as increasing tear secretion and augmenting the rate of re-epithelialisation. Nucleotides and dinucleotides are present in the aqueous humour, and they can modify the production or drainage of the aqueous humour and therefore affect the intraocular pressure. In the retinal space, nucleotides can modify the activity of both neuronal and glial retinal elements in different ways. Some chemically modified nucleotides and dinucleotides can be more active than the natural ones, opening up the possibility of using them for clinical purposes. In particular, compounds designed for dry eye syndrome, ocular hypertension, and retinal detachment are under study with very promising results. In summary, these compounds are becoming more relevant to the understanding of ocular physiology and also as a novel strategy for the treatment of ocular pathologies. Drug Dev. Res. 59:136-145, 2003.