Purpose: Medications of choice to manage elevated intraocular pressure (IOP) are effective but may have systemic effects. A new agent with a distinct pharmacological profile, unoprostone isopropyl, offers a novel approach to control mild to moderately elevated IOP. Preclinical studies have shown that unoprostone has no affinity for PG receptors; it may enhance ocular blood flow by antagonizing ET-1-induced vasoconstriction; it appears to improve aqueous humor outflow. Methods: Five phase III trials evaluated this new agent as monotherapy and adjunctive therapy. Results: The first trial, comparing unoprostone, dorzolamide, and brimonidine as adjuncts to timolol, found that the combination of unoprostone plus timolol was not statistically different; however, more frequent side effects were observed in the dorzolamide and brimonidine groups. A subgroup analysis of a second trial evaluating the efficacy of unoprostone, timolol, and betaxolol found that unoprostone is comparable to betaxolol and has a favorable local safety profile. The third study, which evaluated the effects on pulmonary function in stable asthma patients, found no significant differences between unoprostone and placebo. The fourth study compared the effects of timolol and unoprostone on cardiovascular function in healthy subjects during exercise and found that unoprostone, unlike timolol, exhibited no b-blockade effects. The fifth trial assessed unoprostone in combination with latanoprost and demonstrated additional IOP reductions over latanoprost alone. Conclusion: These studies suggest that the docosanoid unoprostone isopropyl is effective and safe as monotherapy and adjunctive therapy.