Systemic carbonic anhydrase inhibitors are among the most powerful agents to lower intraocular pressure. Unfortunately, their use is frequently accompanied by undesired side effects. Some are due to the relatively large amounts of drug that have to be systemically administered to inhibit the carbonic anhydrase in the ciliary processes. Recently, dorzolamide, a topical carbonic anhydrase inhibitor, has become commercially available for clinical use. This article reviews the development of topical carbonic anhydrase inhibitors with special reference to dorzolamide. When administered three-times daily, dorzolamide lowers intraocular pressure in a clinically useful manner. Ocular side-effects include frequent stinging and burning and allergy can develop. Systemic side effects have not been observed that could definitively be related to inhibition of extraocular carbonic anhydrase. Blood dyscrasias have not yet been observed. Absence of cardiovascular and pulmonary side effects, as can occur with beta adrenergic antagonists, and lack of pupillary and accommodative stimulation, as occur with cholinergic agonists, might make dorzolamide first-line medical treatment for elevated intraocular pressure.