Herpes simplex encephalitis (HSE) remains the most important cause of fatal sporadic encephalitis in man. Caused by herpes simplex virus type 1 (HSV-1), and more rarely by HSV-2, it can have devastating clinical consequences for the patient, especially when the instigation of acyclovir therapy has been delayed by more than 2 days or more. Even with acyclovir treatment, nearly a third of patients may die or suffer significant morbidity. Both host and viral factors may interact to affect the clinical phenotype. Here we consider some of the recently published management guidelines for HSE and comment on various current issues of contention. The latter includes the timing and frequency of cerebrospinal fluid examinations for the polymerase chain reaction detection of HSV, decisions regarding acyclovir therapy including the consequences of delay in its initiation, and the use of corticosteroids in the disease.