Gonococcal keratoconjunctivitis is a potentially devastating infection, because Neisseria gonorrhoeae can cause a rapid, severe, ulcerative keratitis resulting in visual loss. The therapeutic decision making process is complicated by the necessity for prompt, effective parenteral therapy, frequent coinfection with other sexually transmitted diseases, and emergence of antibiotic resistance. Because of the evolving problem of antibiotic resistance and the need for cost containment, the current recommendations of hospitalization for intravenous penicillin may need to be modified. The third generation cephalosporin, ceftriaxone, has properties that suggest it may be the best available antimicrobial agent as a single-dose treatment of gonococcal conjunctivitis. Spectinomycin may be a useful alternative in the penicillin-allergic adult patient.