The incidence of trichomoniasis (Trichomonas vaginalis) in the United States is estimated at 5 million cases annually; chlamydia (Chlamydia trachomatis) at 3 million; gonorrhea (Neisseria gonorrhoeae), 650,000; and syphilis (Treponema pallidum), 70,000. However, most sexually transmitted infections (STIs) are asymptomatic-contributing to underdiagnosis estimated at 50% or more. Diagnosis of an STI signals sexual health risk because an STI facilitates the transmission and acquisition of other STIs, including human immunodeficiency virus (HIV). In fact, comorbid STIs increase patients' susceptibility of acquiring and transmitting HIV by two- to fivefold. Several studies have shown that aggressive STI prevention, testing, and treatment reduces the transmission of HIV. The authors discuss common clinical presentations, screening, diagnosis, and treatment for trichomoniasis, chlamydia, gonorrhea, syphilis, and herpes simplex virus.