Primary angiitis of the central nervous system (PACNS) is a rare form of vasculitis of unknown cause. The mean age of onset is 50 years, and men are affected twice as often as women. Headache and encephalopathy are the most frequent initial symptoms. Stroke or focal symptoms develop in less than 20% of patients at the onset of disease and are uncommon in the absence of headache or encephalopathy. Symptoms or signs of vasculitis outside of the central nervous system are rare; serologic markers of inflammation are typically normal. Magnetic resonance imaging of the brain is abnormal in more than 90% of patients, but the pattern of abnormal findings is not specific. Cerebrospinal fluid analysis is also usually abnormal because of modest, nonspecific elevations in total protein level or white blood cell count. Angiography has a low sensitivity and low specificity. Most patients suspected of having PACNS have another disease. The diagnosis of PACNS is established by brain biopsy. The differential diagnosis of PACNS is broad and includes reversal cerebral vasoconstriction. In contrast to patients with PACNS, patients with reversal cerebral vasoconstriction are more often young women who experience a thunderclap headache and have a normal cerebrospinal fluid analysis. Patients with biopsy-proven PACNS are treated with cyclophosphamide and prednisone.