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Nasopharyngeal carcinoma (NPC) differs from other head and neck cancers in its aetiology, epidemiology and potential therapeutic options. Despite cure for the majority of the patients, challenges still exist in the prevention of disease relapse, treatment of patients with refractory or metastatic NPC and the management of long-term toxicities. This article discusses the specific challenges in pushing the boundaries of NPC treatments further, with an emphasis on prognostic/predictive markers, molecularly targeted therapies, immunotherapies and the areas of interest with regard to long-term toxicities arising from therapeutic interventions.