Panic disorder is a chronic and recurring condition, and there is therefore a need for long-term therapy. This paper reviews data from long-term studies of drug treatment for panic disorder to address issues of whether medication benefits persist, whether improvement can continue over several months or years, the tolerability of long-term treatment, patient selection for long-term treatment, and when and how to stop medication. The main conclusion is that long-term drug treatment of panic disorder is necessary, effective, and safe. Serotonin selective reuptake inhibitors offer benefits of ease of dosing, good tolerability, and no safety or dependence problems; TCAs are often poorly tolerated, and benzodiazepines are associated with dependence problems. Withdrawal from all types of medication should be considered, slow, planned, and individualized; some patients require an indefinite duration of treatment.