Acute retinal necrosis (ARN) is a rare disease that is usually caused by one of the three neurotropic human herpesviruses - herpes simplex virus type 1(HSV-1), HSV-2 and varicella-zoster virus (VZV). Although much is known about the clinical course of the disease and its treatment and about the viruses that cause it, comparatively little is known about its pathogenesis. This article will review the history of ARN, the typical clinical findings, and methods of diagnosis. Information from studies of the mouse model of ARN including development of anterior chamber-associated immune deviation (ACAID) and routes of spread will be reconsidered, and the combined information from human and mouse studies will be discussed to suggest mechanisms that contribute to the pathogenesis of ARN in human patients. Finally, puzzles and questions about the disease will be considered.