Specific phobia is a common, heterogeneous disorder whose central feature is persistent, unreasonable fear of a circumscribed object or situation. This article reviews current etiological theories and empirical data that seem likely to be important in investigating the pathophysiology of this disorder. These include conditioning, modified conditioning, and nonassociative models of phobia development, physiological response to the phobic stimulus, neuroimaging, primate, and biological challenge studies. Pathophysiological hypotheses suggested by recent research on the neurocircuitry of conditioned fear are also discussed. Though specific phobias have been of less public health and clinical interest than other anxiety disorders, their circumscribed nature and possible relationship to conditioned fear may make them a productive subject for research into basic pathophysiology.