Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS) typically begins with progressive visual loss in the third or fourth decade of life followed by focal neurological deficits within 4-10 years. The clinical features of HERNS include strokes, retinopathy, nephropathy, migraine, mood disorders, and dementia. The underlying mechanism of HERNS appears to be a generalized vasculopathy with disruption of the integrity of capillaries and arterioles. Fluorescein angiograms clearly show retinal vasculopathic changes. That the intracerebral lesions show contrast enhancement on magnetic resonance imaging (MRI) indicates break down in the blood-brain barrier. The surrounding edema in a vasogenic pattern also suggests increased capillary permeability. At the present time there is no known treatment that is effective in patients with HERNS. However, corticosteroids have been useful to decrease cerebral edema and may even be life-saving in patients with large edematous lesions.