Melatonin, an indoleamine secreted mainly by the pineal gland, is known to modulate a wide range of circadian functions. However, this neurohormone is also synthesized within the eye and acts directly on ocular structures to mediate a variety of physiological processes. This review is focused on the role and therapeutic potential of melatonin in ocular diseases. We summarize data indicating that melatonin may represent a powerful tool to counteract ocular dysfunctions such as uveitis, glaucoma, age-related macular degeneration, and diabetic retinopathy. A search strategy was conducted to identify studies in PubMed (January 1990 to September 2017). In particular, we included experimental studies, clinical trials, and reviews to provide suitable insights and elucidations regarding the action of melatonin on age-related ocular disorders. Literature data suggest that melatonin could potentially protect ocular tissues by decreasing the production of free radicals and pro-inflammatory mediators. Additionally, melatonin appears to be safe and well-tolerated, even at high doses, and no adverse/side effects were reported. Although this topic remains under intense investigation, we can conclude that melatonin, as a single agent or in combination with other drugs, is an attractive pharmacological candidate for age-related ocular diseases.