Epididymo-orchitis is a commonly encountered condition with a reported incidence of 2.45 cases per 1000 men in the United Kingdom. This 2016 International Union against Sexually Transmitted Infections guideline provides up-to-date advice on the management of this condition. It describes the aetiology, clinical features and potential complications, as well as presenting diagnostic considerations and clear recommendations for management and follow-up. Early diagnosis and management are essential, as serious complications can include abscess formation, testicular infarction and infertility. Recent epidemiological evidence suggests that selection of fluoroquinolone antibiotics with anti-Chlamydial activity is more appropriate in the management of sexually active men in the over 35 years age group.