Sexually transmissible diseases (STDs) remain a major health issue worldwide, with approximately 300 million new cases annually. STDs caused by bacteria can be treated with antibiotics, although the susceptibility pattern of many etiologic microbes has changed over the past few decades. Syphilis remains best managed with single-dose benzathine penicillin G. Other single-dose antibiotic regimens for lues are either associated with clinical failure or of uncertain dosage. However, single-dose azithromycin and ceftriaxone are suitable for chancroid. Lymphogranuloma venereum, reemergent as a cause of proctitis, is treated with prolonged courses of doxycycline or minocycline. Trimethoprim-sulfamethoxazole has replaced tetracycline derivatives as preferred treatment for donovanosis in many regions. Parenteral cephalosporins, such as ceftriaxone, cefotaxime, and ceftizoxime, are initial interventions for disseminated gonococcemia. Pending culture results, genital bite wounds (often consisting of deep, painful ulcerations) should be treated with high-dose amoxicillin-clavulanic acid.