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The WHO global health sector strategy on sexually transmitted infections, 2016–2021, endorsed by the World Health Assembly in 2016, aims to eliminate STIs as a public health threat by 2030. In 2019, WHO published estimates of new cases of chlamydia, gonorrhoea, syphilis and trichomoniasis. Recent changes in the epidemiology of STIs and progress in prevention, diagnosis and treatment of STIs and HIV have necessitated changes in approaches to STI prevention and management. To address these STIs, the most widely used approach in clinical settings is the syndromic management of STIs. In most resource-limited settings, the syndromic management flow charts are still the standard of care where laboratory diagnosis is not available or is hard to access. The objectives of these guidelines are to provide updated, evidence-informed clinical and practical recommendations on the case management of people with symptoms of STIs; and to support countries in updating their national guidelines for the case management of people with symptoms of STIs. These guidelines include the management of symptomatic infections related to urethral discharge syndrome, including persistent urethral discharge syndrome; vaginal discharge syndrome, including persistent vaginal discharge; anorectal infection; genital ulcer disease syndrome; and lower abdominal pain syndrome. These guidelines are intended for programme managers for STI prevention and control at the national level and the health-care providers at the frontline – primary, secondary and tertiary health care.