These guidelines for the treatment of persons who have sexually transmitted diseases (STDs) were developed by CDC after consultation with a group of professionals knowledgeable in the field of STDs who met in Atlanta, Georgia, during April 19-21, 2005. The information in this report updates the Sexually Transmitted Diseases Treatment Guidelines, 2002 (MMWR 2002;51[No. RR-6]). Included in these updated guidelines are an expanded diagnostic evaluation for cervicitis and trichomoniasis; new antimicrobial recommendations for trichomoniasis; additional data on the clinical efficacy of azithromycin for chlamydial infections in pregnancy; discussion of the role of Mycoplasma genitalium and trichomoniasis in urethritis/cervicitis and treatment-related implications; emergence of lymphogranuloma venereum protocolitis among men who have sex with men (MSM); expanded discussion of the criteria for spinal fluid examination to evaluate for neurosyphilis; the emergence of azithromycin- resistant Treponema pallidum; increasing prevalence of quinolone-resistant Neisseria gonorrhoeae in MSM; revised discussion concerning the sexual transmission of hepatitis C; postexposure prophylaxis after sexual assault; and an expanded discussion of STD prevention approaches.