AIMS: Pathological gambling (PG) is a relatively common and often disabling psychiatric condition characterized by intrusive urges to engage in deleterious gambling behavior. Although common and financially devastating to individuals and families, there currently exist no formally approved pharmacotherapeutic interventions for this disorder. This review seeks to examine the history of medication treatments for PG. METHODS: A systematic review of the 18 double-blind, placebo-controlled pharmacotherapy studies conducted for the treatment of pathological gambling was conducted. Study outcome and the mean dose of medication administered was documented in an effort to determine a preferred medication choice in this population. RESULTS: A variety of medication classes have been examined in the treatment of PG with varying results. Antidepressants, atypical antipsychotics, and mood stabilizers have demonstrated mixed results in controlled clinical trials. Although limited information is available, opioid antagonists and glutamatergic agents have demonstrated efficacious outcomes, especially for individuals with PG suffering from intense urges to engage in the behavior. CONCLUSIONS: Given that several studies have demonstrated their efficacy in treating the symptoms associated with PG, opioid antagonists should be considered the first-line treatment for PG at this time. Most published studies, however, have employed relatively small sample sizes, are of limited duration, and involve possibly non-representative clinical groups (e.g., those without co-occurring psychiatric disorders. Response measures have varied across studies. Heterogeneity of PG treatment samples may also complicate identification of effective treatments. Identification of factors related to treatment response will help inform future studies and advance treatment strategies for PG.