The Centers for Disease Control and Prevention recently published revised guidelines for the prevention and treatment of sexually transmitted diseases. One new treatment strategy is the use of azithromycin as a primary, rather than alternative, medication for pregnant women with Chlamydia trachomatis infection. Quinolone-resistant Neisseria gonorrhoeae infection continues to increase in the United States; therefore, quinolones are no longer recommended for treatment of this infection. Expedited partner therapy gives physicians another option when addressing the need to treat partners of persons diagnosed with N. gonorrhoeae or C. trachomatis infection. Tinidazole is now available in the United States and can be used to manage trichomoniasis, including trichomoniasis resistant to metronidazole. Shorter courses of antiviral medication can be used for episodic therapy of recurrent genital herpes. Because of increasing resistance, close follow-up is required if azithromycin is used as an alternative treatment in the management of primary or secondary syphilis. Unexpected increases in the rates of lymphogranuloma venereum have occurred in The Netherlands, and physicians should remain vigilant for symptoms of this disease in the United States.