Although pathological gambling is a relatively common disorder, there exists only limited information regarding the effectiveness of pharmacotherapy for this illness. This study examines which medications may be effective, dose and duration of medication trials needed to achieve response, and possible predictors of response. Using a chart review, 50 adult outpatients with DSM-IV pathological gambling treated in clinical practice were assessed regarding response to a variety of medications, including augmentation strategies, and response to concomitant psychotherapy. All subjects received pharmacotherapy for gambling symptoms. Thirty-nine (78%) achieved response to medication treatment. Mean duration of treatment needed for response was 104.9 +/- 85.0 days. Of those treated with an adequate trial of naltrexone as monotherapy, 90.9% were responders, whereas only 45.5% of those treated with an adequate trial of an SSRI achieved response. Patients with poorer social and occupational functioning due to urges and thoughts about gambling were less likely to respond to medication. These findings from a clinical setting suggest that a majority of pathological gamblers improve with medication treatment. Naltrexone, or augmentation of naltrexone with an SSRI, appears to be most effective in relieving gambling symptoms.