Methadone has been used as a pharmacotherapy for the treatment of opiate dependence since the mid-1960s. Many studies examining the benefits of methadone maintenance treatment (MMT) for opiate dependence have documented a significant reduction in both criminal behavior and the use of other opiates. Nevertheless, emerging evidence suggests that MMT may impair cognitive function. However, it is unclear as to the part methadone dose, duration of MMT or plasma level may play in any observed deficits. Given the large number of people enrolled in MMT world-wide and the potential for deficits in cognitive function, a systematic review of the research investigating the association between MMT and cognitive function seemed warranted. The following databases were searched with a combination of free-text and thesaurus terms (methadone AND cognition): MEDLINE In-Process, EMBASE, PsycINFO and EBM Reviews-Cochrane Central Register of Controlled Trials. Seventy-eight articles were retrieved of which 35 met the inclusion criteria. The majority of research suggests that MMT is associated with impaired cognitive function and that deficits extended across a range of domains. However, caution is required when interpreting these results due to the methodological limitations associated with many studies. Further research that includes a combination of psychological and physiological measures within well-controlled group comparison studies is required to more accurately assess which cognitive domains are affected.