Trichomonas vaginalis is the most prevalent nonviral sexually transmitted infection, affecting an estimated 3.7 million women and men in the United States. Health disparities are prominent in the epidemiology of this infection, which affects 11% of women aged ≥40 years and a disproportionately high percentage of black women. Particularly high prevalences have been identified among sexually transmitted disease (STD) clinic patients and incarcerated individuals. This article reviews and updates scientific evidence in key topic areas used for the development of the 2015 STD Treatment Guidelines published by the Centers for Disease Control and Prevention. Current evidence is presented regarding conditions associated with Trichomonas vaginalis infection, including human immunodeficiency virus (HIV) and pregnancy complications such as preterm birth. Nucleic acid amplification tests and point-of-care tests are newly available diagnostic methods that can be conducted on a variety of specimens, potentially allowing highly sensitive testing and screening of both women and men at risk for infection. Usually, trichomoniasis can be cured with single-dose therapy of an appropriate nitroimidazole antibiotic, but women who are also infected with HIV should receive therapy for 7 days. Antimicrobial resistance is an emerging concern.