New insights have helped improve our skills in prevention, epidemiology, diagnosis, and treatment of sexually transmitted diseases. Among the "pearls" in this article, we discuss diagnostic options, therapeutic decisions, and recurrence of infection with Chlamydia. For gonorrhea, we address emerging fluoroquinolone resistance and penile edema. Regarding vaginal diseases, we discuss the value of vaginal pH in differentiating causes of vaginal discharge, the diseases in which male partners do or do not need treatment, and the approach to recurrent vulvovaginal candidiasis. For herpes, we consider current epidemiology, asymptomatic shedding, clinical manifestations, and acyclovir resistance. Regarding syphilis, we address the importance and interpretation of nontreponemal serology, as well as the approach to treatment nonadherence. For genital warts, we discuss when to perform a biopsy and the role of human papillomavirus in anal carcinoma.