Although most bacterial sexually transmitted diseases (STDs) can be effectively treated, currently available regimens are far from ideal. Increasingly widespread plasmid-mediated resistance to the penicillins limits the use of these agents in the treatment of Neisseria gonorrhoeae and Hemophilus ducreyi infections. Chromosomally mediated antimicrobial resistance to the tetracyclines, penicillins, erythromycins, and sulfonamides further limits therapeutic options in the treatment of gonorrhea, and plasmid-mediated resistance to sulfonamides and tetracyclines is frequent in H. ducreyi infections. In patients with Chlamydia trachomatis infections, effective regimens that can more easily be complied with (shorter duration, less frequent dosing) are needed, as are effective alternative regimens for use in pregnancy and in infants. In selected STDs that are polymicrobial (pelvic inflammatory disease and bacterial vaginosis, for example) or that often present simultaneously (gonorrhea-chlamydia, gonorrhea-syphilis, chancroid-syphilis), single-drug regimens that are effective against several genital pathogens would be ideal. Only limited therapeutic alternatives are available for some STDs, especially in pregnant women or in patients with penicillin allergy. Thus, antimicrobial resistance, drug toxicity, poor compliance, limited alternatives in pregnancy or allergy, and the lack of single agents possessing a broad spectrum of activity against multiple genital pathogens limit currently available therapy.