Topically administered ophthalmic medications are capable of attaining clinically important serum concentrations, as evidenced by the variety of systemic side effects they can produce. These drugs are therefore also capable of interacting with other drugs administered orally and intravenously. This is especially important when medications are administered to an elderly population, who are often receiving multiple medications. The Physician's Desk Reference and the United States Pharmacopeia Drug Information directory contain numerous warnings of potential interactions between topical glaucoma medications and systemically administered drugs. Unfortunately, literature supporting such interactions is limited, both in quantity and quality, being anecdotal in many cases. This report summarizes available information regarding the nonocular interactions between topical ophthalmic glaucoma medications and other systemically administered medications. Clinical evidence of these interactions is lacking in many cases.