Sixty years after its discovery as the first human tumour virus, Epstein-Barr virus (EBV)-specific therapies and vaccines have entered clinical trials. These might not only be applicable for EBV-associated malignancies, where the virus was originally discovered, but also to immunopathologies, including the autoimmune disease multiple sclerosis, which might be triggered in susceptible individuals by primary EBV infection. This Review discusses the surprisingly large spectrum of diseases that EBV seems to cause, as well as which of these might be treated by the therapeutic approaches that are currently being developed or are already clinically applied. New pharmacological inhibitors, antibody therapies, adoptive T cell therapies and active vaccinations are beginning to offer possibilities to target the various EBV infection programmes that are associated with different diseases. These novel developments might allow us to specifically target EBV rather than its host cells in virus-associated pathologies.