Sexually transmitted infections (STIs) cause tremendous morbidity, great costs, and numerous avoidable deaths in the United States each year. STIs in men can present as discharge, ulcers, papules, infestations, or systemic disease, but most commonly STIs present without any symptoms. Molecular techniques, single-dose antibiotics and antivirals, and patient-administered therapies present opportunities for enhanced diagnosis and treatment. Screening for STIs should be part of all primary care practices, specifically targeting high-risk persons and those diagnosed with another STI.