Primary angiitis of the central nervous system (PACNS) is a rare disorder that must be differentiated from secondary CNS vasculitides, reversible cerebral vasoconstriction syndromes, and other vascular disorders. Because of the rarity of PACNS, no controlled trials have been performed, thereby precluding an evidence-based approach to therapy. PACNS has been considered to have three major subsets, as defined by clinical, laboratory, angiographic, and pathologic findings: granulomatous angiitis of the central nervous system (GACNS), benign angiopathy of the central nervous system (BACNS), and atypical PACNS. Approximately 5% of cases may present as a tumor-like mass lesion. Because the subset of patients with GACNS has a more guarded prognosis, treatment with high-dose glucocorticoids and cyclophosphamide is necessary. All patients with atypical PACNS should be treated with high-dose glucocorticoids initially. The use of additional immunosuppressive agents depends on the severity of the initial presentation, the ability to achieve remission with glucocorticoid monotherapy, and the occurrence of relapse upon glucocorticoid tapering. PACNS mass lesions can regress completely with immunosuppressive therapy, and therefore, surgical excision may be avoided. Patients with BACNS should be treated with a calcium channel blocker (eg, verapamil) with or without a short course of glucocorticoids. These patients should not receive additional immunosuppressive therapies such as cyclophosphamide. This reflects the fact that BACNS is now more correctly considered as a reversible cerebral vasoconstriction syndrome (RCVS) and not as a true vasculitis. However, a patient initially diagnosed with RCVS that demonstrates incomplete resolution of angiographic findings after 3 to 4 months should be re-evaluated for alternative diagnoses, including PACNS.