This chapter deals with “unusual” causes of ischemic stroke to highlight clues in the history, on examination and on imaging, which should serve as “red flags” that something unusual may be underlying the patient’s presenting symptoms. It divides the unusual causes of stroke into several subcategories including arterial injury; inflammatory vasculopathies and syndromes; congenital arteriopathies; hematological disorders; stroke as a result of systemic illnesses; genetic causes; and others. Cervical arterial dissections are considerably more common than intracranial dissections and their presentations are different enough that they should be considered separately. The most common vasculitis involving the brain is the temporal arteritic form of giant-cell arteritis (GCA), although it is fundamentally a systemic vasculitis. Posterior reversible encephalopathy syndrome (PRES) can present with focal neurologic deficits and so mimic ischemic or hemorrhagic stroke or transient ischemic attack. A stroke is deemed cryptogenic if there are no evident direct cause or high-risk features for recurrence.