Disordered gambling is a public health concern associated with detrimental consequences for affected individuals and social costs. Currently, opioid antagonists are considered the first-line treatments to reduce symptoms of uncontrolled gambling. Only recently, glutamatergic agents and combined pharmacological and psychological treatments have been examined appearing promising options for the management of gambling disorder. A multilevel literature search yielded 34 studies including open-label and placebo-controlled trials totaling 1340 participants to provide a comprehensive evaluation of the short- and long-term efficacies of pharmacological and combined treatments. Pharmacological treatments were associated with large and medium pre-post reductions in global severity, frequency, and financial loss (Hedgess g: 1.35, 1.22, 0.80, respectively). The controlled effect sizes for the outcome variables were significantly smaller (Hedgess g: 0.41, 0.11, 0.22), but robust for the reduction of global severity at short-term. In general, medication classes yielded comparable effect sizes independent of predictors of treatment outcome. Of the placebo controlled studies, results showed that opioid antagonists and mood stabilizers, particularly the glutamatergic agent topiramate combined with a cognitive intervention and lithium for gamblers with bipolar disorders demonstrated promising results. However, more rigorously designed, large-scale randomized controlled trials with extended placebo lead-in periods are necessary. Moreover, future studies need to monitor concurrent psychosocial treatments, the type of comorbidity, use equivalent measurement tools, include outcome variables according to the Banff, Alberta Consensus, and provide follow-up data in order to broaden the knowledge about the efficacy of pharmacological treatments for this disabling condition.