Background: Demand for treatment for amphetamine use is increasing internationally. Establishing effective pharmacotherapy provides broader treatment options for people who are dependent on amphetamine and may encourage engagement in evidence-based behavioral treatment. This study aimed to identify medicines that have potential in improving treatment outcomes for people who are dependent on amphetamines. Methods: Medline, PsycINFO, Embase and the Cochrane Database of Systematic Reviews were searched from 1997 to 2012 and again from 2013 to 2016. Studies on medications for amphetamine/methamphetamine dependence treatment were selected and assessed by two independent researchers. A meta-narrative review approach was used to synthesize results. Results: A total of 49 studies investigating 20 potential pharmacotherapies were eligible for inclusion. Of these, 35 studies related to 33 level II quality randomized controlled trials (RCTs). Five medications were subject to multiple RCTs. Four of these medicines demonstrated some limited evidence of benefit for reducing amphetamine use: methylphenidate (as reported in three studies), buprenorphine (in three studies), modafinil (two studies), and naltrexone (one study). Four RCTs of dexamphetamine suggest its benefit on secondary outcomes such as treatment retention, but not for reducing amphetamine use. Six other medicines indicate the potential for efficacy, but the number of studies is too small to draw conclusions. Conclusions: No medicine has as yet demonstrated sufficient, consistent evidence of effectiveness to support its use in routine treatment. High study drop-out and poor medication adherence limits the strength of evidence and raises important clinical questions about how to improve treatment engagement and outcomes.