There are many different and diverse causes of central nervous system (CNS) vasculitis, and many nonvasculitic disorders that often mimic CNS vasculitis. CNS vasculitis is usually suspected clinically with compatible or suggestive angiographic findings, but a definitive diagnosis is not possible without biopsy confirmation, especially with CNS vasculitis mimickers. Primary CNS vasculitis, although relatively uncommon, is most important because of its overall unfavorable prognosis. Secondary CNS vasculitis occurs in association with a long list of systemic vasculitic and nonvasculitic disorders with variable brain biopsy findings. Because of the focal and segmental distribution of CNS vasculitis, a positive biopsy is diagnostic for the disease demonstrated, but a single isolated negative biopsy does not necessarily exclude primary or secondary CNS vasculitis.