This article explains the approach to managing a patient with herpes simplex virus encephalitis. Acute encephalopathy is a common and often intimidating presentation in an acute general medical setting. Application of key principles will enable the generalist to take life-saving action before obtaining any specialist input. Viral infection is the most common cause (48.2%) of encephalitis; another large group is cases of autoimmune aetiology. Early diagnosis of encephalitis is crucial to ensure that the right treatment is given on time. Guidelines on the management of viral encephalitis were published by the British Association of Neurologists and British Infection Association ( Solomon et al, 2012 ), but adherence to these standards by clinicians has been found to be suboptimal ( Han and Coebergh, 2017 ). This puts lives in danger, in the context of a treatable, serious, acute presentation. Although viral infection is the most common cause of encephalitis, an awareness of rarer forms of autoimmune encephalitis is necessary. The differential diagnosis of autoimmune encephalitis is important because the disease is potentially treatable with immunosuppressive agents. Paraneoplastic limbic encephalitis may present months or years before the detection of a tumour.