WHO has published the first-ever guidance on the clinical management of diphtheria. The only previously available guidance was an operational protocol. The new guidance followed the rigorous process for developing guidance at WHO. It addresses the use of Diphtheria Antitoxin (DAT) in the treatment of diphtheria. There is a worldwide shortage of DAT and evidence based recommendations on the use of DAT were requested by many Member States. The guidance also includes new recommendations on antibiotics. In patients with suspected or confirmed diphtheria, WHO recommends using macrolide antibiotics (azithromycin, erythromycin) rather than penicillin antibiotics. This clinical practice guideline has been rapidly developed recognizing the global increase in diphtheria outbreaks. Outbreaks of diphtheria in Nigeria, Guinea and neighbouring countries in 2023 have highlighted the urgent need for evidence-based clinical practice guidelines for the treatment of diphtheria. Given the sporadic nature of outbreaks, many clinicians in the affected regions have never managed acute diphtheria and its related complications. Diphtheria remains a neglected disease and vaccination is the top priority. At the same time, for patients with diphtheria, access to antibiotics, DAT and supportive care can be lifesaving.