The role of serotonin in psychiatry has been the focus of speculation for several decades. The literature since 1966 is reviewed (and referenced) and five organizing questions are identified: (1) What are the major hypotheses regarding the involvement of the serotonin system in panic disorder? (2) Is there a serotonin system defect associated with panic disorder? (3) Is a serotonin system defect the cause of panic disorder? (4) Are the 5-HT1A, agonists and the 5-HT2 antagonists effective in this condition? (5) Are serotonin selective uptake inhibitors (SSUIs) effective in panic disorder via the serotonin system or some other mechanism? Though the role of the serotonin system in panic disorder and social phobia is uncertain there is increasing agreement that SSUIs effectively treat panic disorder but further double-blind placebo-controlled studies are needed.