Brain arteriovenous malformations (AVMs) are a rare but important cause of intracranial hemorrhage (ICH) in young adults. In this paper, we review both human and animal studies of brain AVM, focusing on the: (1) natural history of AVM hemorrhage, (2) genetic and expression studies of AVM susceptibility and hemorrhage, and (3) strategies for development of a brain AVM model in adult mice. These data target various mechanisms that must act in concert to regulate normal angiogenic response to injury. Based on the various lines of evidence reviewed in this paper, we propose a "response-to-injury" model of brain AVM pathogenesis.