A revised national guideline for the management and control of sexually transmitted infections (STIs) has recently been published by the National Department of Health according to the Essential Drugs List. Since 2004, there has been a marked rise in resistance to ciprofloxacin among Neisseria gonorrhoeae isolates in several South African cities, requiring a change from quinolones to cephalosporins to treat presumptive gonorrhoea. In keeping with WHO recommendations, acyclovir has been added as part of first-line therapy for the management of genital ulceration. The national guideline has been revised accordingly in order to improve management of several key STI syndromes.