The early information on the clinical efficacy, safety, and tolerability of brimonidine 0.2% were obtained from studies that compared brimonidine monotherapy with timolol and betaxolol. These studies showed its intra-ocular pressure lowering efficacy to be comparable with timolol and superior to betaxolol. The data from the timolol studies showed consistent results after four years. These findings have been confirmed by additional studies in the clinical setting. More recently, several clinical trials have been completed investigating the role of brimonidine as adjunctive medication to beta-blockers and as replacement therapy to other intraocular pressure lowering compounds. When added to beta-blockers, brimonidine is superior to dorzolamide, similar in efficacy but better tolerated than pilocarpine, and more predictable than latanoprost. Data from replacement studies have indicated that there may be advantages in replacing rather than adding medications in the treatment of glaucoma.