Glaucoma is a neurodegenerative pathology that affects the optic nerve producing blindness. This disease is often a consequence of an abnormal increase of intraocular pressure (IOP) due to a reduction in the ability of the eye to drain a transparent fluid termed aqueous humour. The dynamics of the aqueous humour is highly controlled by the autonomic nervous system, mainly the sympathetic, regulating its production and parasympathetic controlling the evacuation of aqueous humour. This has led pharmaceutical companies to develop chemicals which, by acting via different targets can substantially reduce IOP. Parasympathomimetics, adrenergic antagonists, plus eventually adrenergic agonists, are commonly used for the reduction of IOP and therefore for treatment of glaucoma. New substances linked to the nervous system that innervates the eye are emerging as interesting candidates. Nucleotides, commonly costored with catecholamines or acetylcholine or the indole melatonin, present interesting properties reducing IOP. Moreover new technological ideas such as the use of siRNA (small interference RNA) to silence protein expression demonstrate the relevance of this method to approach ocular hypertension and glaucoma from a different point of view. These three main groups of molecules: nucleotides, melatonins and siRNAs, are reviewed since they appear as firm candidates for the treatment of glaucoma in the near future.