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Nature has always provided an unlimited source of biologically-active compounds. Since the beginning of mankind, humans have sought resources in fauna and flora to treat eye diseases. However, it was only after the Industrial Revolution that extracts of plants and substances of animal origin could be used safely, as has been determined by controlled interventional studies. Two major challenges faced by ocular pharmacology are the following: developing drugs that are able to reduce blindness due to glaucoma; and controlling the pain associated with eye surgery. The search for a drug that effectively lowers intraocular pressure and controls the progression of glaucoma has led to the development of various ocular hypotensive agents, such as physostigmine from the Physostigma venenosum plant. The anesthetic properties of cocaine, extracted from Erythroxylon coca, finally enabled surgical procedures in the eye. Several new natural compounds have been investigated in an attempt to identify substances with the potential to provide additional benefits to eye tissue and vision. Emerging evidence of anti-inflammatory, wound-healing, antimicrobial, antioxidant, antitumor, and antiangiogenic properties attributed to plant extracts and animal tissues has encouraged more investment in research in this area. Despite technological advances in synthesizing drugs, the pharmaceutical industry still seeks new active compounds from natural sources as well as from revisiting already-established naturally derived compounds. Although a large number of naturally-occurring compounds is known, this review article focuses on the bioactive substances …