PANDAS is an acronym for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection. As defined, the criteria include prepubertal children with either a tic or obsessive-compulsive disorder in whom a Group A beta-hemolytic streptococcal infection (GABHS) triggers the abrupt onset or exacerbation of tics/obsessive-compulsive behaviors. Pathophysiologically, it is proposed that antibodies produced against GABHS cross-react with neuronal cells, in a process involving molecular mimicry. Although PANDAS has received widespread notoriety, the existence of this condition has been questioned. This commentary reviews clinical and laboratory issues pertinent to the diagnosis of this entity. We conclude that PANDAS is an intriguing hypothesis that requires further confirmation.