Panic disorder is a chronic, disabling condition that is often associated with a need for long-term clinical treatment. While a variety of pharmacotherapy options, including tricyclic antidepressants, selective serotonin reuptake inhibitors, and benzodiazepines, are effective in reducing symptoms in the acute phase, a significant number of patients do not fully respond to initial treatment, and a large majority of patients experience relapse after medication discontinuation. Optimal long-term treatment of panic disorder involves attention to adequate medication dosing and adequate duration of treatment to achieve maximum improvement before discontinuing. Recent reports suggest the efficacy of adjunctive pharmacotherapies and combining pharmacotherapy with behavioral therapy to improve treatment response. Further research is necessary to determine the long-term effectiveness of these multifaceted treatment strategies among patients suffering from refractory panic disorder.