Objectives To illustrate that acute, even dramatic, demyelination of the central nervous system and encephalitis can occur after viral i.e. influenza A/H1N1 vaccination or infection. Patients and methods We describe a case of encephalitis/acute disseminated encephalomyelitis associated with vaccination against influenza A/H1N1 and review the available literature. Results We report a case of a 26-year-old female who developed symptoms of acute encephalitis 5 days after vaccination against the pandemic 2009 A/H1N1 influenza. MRI of the brain showed confluent T2-hyperintense signal intensity changes in the deep white matter which further confirmed the diagnosis of encephalitis/acute disseminated encephalomyelitis. Despite therapy with immunoglobulins and corticosteroids, her persistent vegetative state continued. In light of the dramatic cause of this case, we reviewed all 21 other previously reported cases of central nervous system demyelination related to H1N1 vaccination and/or infection. Conclusions The available data suggest that even severe central nervous system demyelination i.e. acute encephalitis/disseminated encephalomyelitis and transverse myelitis may very rarely be associated with vaccination against novel influenza A/H1N1 or with A/H1N1 infection itself.