Susac’s syndrome is the clinical triad of encephalopathy, branch retinal artery occlusions and sensorineural hearing loss. It is believed to be an immune-mediated endotheliopathy of small vessels. We report a 23 year-old female who presented with a seventeen-day history of retro-bulbar headache, photophobia and vomiting on a background of recent termination of pregnancy. Her initial examination revealed encephalopathy without fever or meningism. She deteriorated rapidly with worsening cognition, drowsiness, urinary incontinence and a generalized seizure. Brain MRI showed multiple foci of restricted diffusion and abnormal T2 signal in the deep white matter and right corpus callosum. In addition, there were nodular areas of leptomeningeal enhancement, particularly over the cerebellum. CSF contained 8 lymphocytes and markedly elevated protein (2.9 g/L). Relevant infective and autoimmune investigations were negative. PET showed marked hypermetabolism in the right cerebellar hemisphere and left parahippocampal gyrus. Brain biopsy revealed mild, non-specific perivascular inflammation. She responded well to corticosteroids but further deteriorated and, for the first time, complained of deafness and tinnitus. Audiometry showed bilateral moderate low frequency hearing loss. Ophthalmic examination and fluoroscein angiography revealed branch retinal arterial occlusions in both eyes confirming Susac’s syndrome. The patient exhibited dramatic improvement within twenty-four hours after receiving a single dose of the tumour necrosis factor (TNF) inhibitor monoclonal antibody, infliximab (5mg/kg). She was subsequently treated with intravenous immunoglobulin, cyclophosphamide, aspirin and nifedipine with sustained benefits at four months. This is the first report that infliximab may be a useful adjunct to existing therapy in Susac’s syndrome.