Vaginal discharge is a common presenting symptom among adolescents and young adult females, with a large differential diagnosis consisting of infectious and noninfectious etiologies. Sexually transmitted infections (STIs) such as chlamydia and gonorrhea are remarkably common among adolescent females and may present with vaginal discharge or irregular menstrual bleeding, although many infections are asymptomatic. Untreated, the causal agents of chlamydia and gonorrhea are easily transmitted to sexual partners. In females, the infection can ascend into the upper genital tract, where complications can include infertility and chronic pelvic pain. Yearly screening of all sexually active women less than 25 years of age is recommended, as is screening of older women at increased risk for infection. Although vaginal discharge can be distressing for patients, the most common cause is actually a benign, noninfectious condition known as physiologic leukorrhea. Providers should use a systematic approach consisting of a comprehensive history including a comprehensive sexual history, detailed physical examination, and results of diagnostic laboratory tests to determine the underlying etiology. Infectious etiologies of vaginal discharge should be treated according to the Centers for Disease Control and Prevention’s Sexually Transmitted Diseases Treatment Guidelines, revised most recently in 2021. Partners exposed to an STI should also receive appropriate treatment empirically along with risk reduction counseling.