Previous reviewers have concluded that opioids cause dose-related impairment in opioid-naive volunteers on psychomotor skills related to driving. Data relating to opioid-dependent/tolerant patients have not yet been reviewed. To determine what evidence, if any, exists for or against opioid-related driving skill impairment in opioid-dependent/tolerant patients, we performed a structured evidence-based review of all available studies addressing the issue of whether opioid-dependent/tolerant patients are impaired in driving-related skills. A computer and manual literature search for studies relating to opioid-dependent/tolerant patients and driving-related skills produced 48 relevant reports. These references were reviewed in detail, sorted, and placed into tabular form according to the following subject areas: (1) psychomotor abilities studies; (2) cognitive function studies; (3) effect of opioid dosing on psychomotor abilities studies; (4) motor vehicle driving violations and motor vehicle accident studies; and (5) driving impairment as measured in driving simulators and off/on road driving studies. For each topic area, each study was categorized for the type of study it represented according to guidelines developed by the Agency for Health Care Policy Research (AHCPR). The strength and consistency of the evidence in each subject area also then was categorized according to AHCPR guidelines and a quantitative method. This evidence-based review indicated the following: (1) There was moderate, generally consistent evidence for no impairment of psychomotor abilities of opioid-maintained patients; (2) There was inconclusive evidence on multiple studies for no impairment on cognitive function of opioid- maintained patients; (3) There was strong consistent evidence on multiple studies for no impairment of psychomotor abilities immediately after being given doses of opioids; (4) There was strong, consistent evidence for no greater incidence in motor vehicle violations/motor vehicle accidents versus comparable controls of opioid-maintained patients; and (5) There was consistent evidence for no impairment as measured in driving simulators off/on road driving of opioid-maintained patients. Based on the above results, it can be concluded that the majority of the reviewed studies appeared to indicate that opioids do not impair driving-related skills in opioid-dependent/tolerant patients. This evidence was consistent in four out of five research areas investigated, but inconclusive in one. As such, additional controlled studies are required. Until more data are available, however, physicians may wish to consider the approach to this problem recommended in this review.