Multiple viruses have been identified as causative agents in acute retinal necrosis (ARN). Retinal biopsies, analysis of intraocular antibody synthesis, and polymerase chain reaction (PCR) have identified varicella zoster virus, herpes simplex virus types 1 and 2, and cytomegalovirus. The differential diagnosis of ARN includes atypical ocular toxoplasmosis, some white dot syndromes, and other forms of retinal vasculitides such as Behçet's disease. Because therapeutic intervention varies greatly in these acute situations, identification of the causative agent is essential. Serology is rarely helpful, whereas analysis of aqueous humor or vitreous samples provides clues to the etiology. Aqueous humor antibody testing and PCR have demonstrated excellent diagnostic power with high sensitivity and high specificity. This review is intended to provide an overview of the diagnostics and differential diagnosis of this rare but important disorder.