The clinical manifestations of central nervous system (CNS) vasculitis are highly variable. In the absence of a positive CNS biopsy, CNS vasculitis is particularly suspected when markers of both vascular disease and inflammation are present. To facilitate the clinical and therapeutic approach to this rare condition, CNS vasculitis can be classified according to the size of the involved vessels. Vascular imaging is used to identify medium vessel disease. Small vessel disease can only be diagnosed with a CNS biopsy. Medium vessel vasculitis usually presents with focal neurological signs, while small vessel vasculitis more often leads to cognitive deficits, altered level of consciousness and seizures. Markers of CNS inflammation include cerebrospinal fluid pleocytosis or elevated protein levels, and vessel wall, parenchymal or leptomeningeal enhancement. The broad range of differential diagnoses of CNS vasculitis can be narrowed based on the disease subtype. Common mimickers of medium vessel vasculitis include intracranial atherosclerosis and reversible cerebral vasoconstriction syndrome. The diagnostic workup aims to answer two questions: is the neurological presentation secondary to a vasculitic process, and if so, is the vasculitis primary (i.e., primary angiitis of the CNS) or secondary (e.g., to a systemic vasculitis, connective tissue disorder, infection, malignancy or drug use)? In primary angiitis of the CNS, glucocorticoids and cyclophosphamide are most often used for induction therapy, but rituximab may be an alternative. Based on the available evidence, all patients should receive maintenance immunosuppression. A multidisciplinary approach is necessary to ensure an accurate and timely diagnosis and to improve outcomes for patients with this potentially devastating condition.