Opioids are the recommended form of analgesia for patients with persistent cancer pain and regular dosing 'by the clock' is advocated in many international guidelines on cancer pain management. The development of sustained release opioid preparations has made regular dosing easier for patients. However, patients report that the intensity and impact of their cancer pain varies considerably day to day, and many try to find a trade-off between acceptable pain control and impact of cognitive (and other) adverse effects on daily activities. In acute care settings, (eg post-operative) as needed dosing and other opioid sparing approaches have resulted in better patient outcomes compared with regular dosing. The aim of this study was to determine whether regular dosing of opioids was superior to as needed dosing for persistent cancer pain. We systematically searched for randomised controlled trials that directly compared pain outcomes from regular dosing of opioids with as needed dosing in adult cancer patients. We identified 4347 records, 25 RCTs meet the inclusion criteria, nine were included in the review and 7 of these included in meta-analysis. We found no clear evidence demonstrating superiority of regular dosing of opioids compared with as needed dosing in persistent cancer pain and regular dosing was associated with significantly higher total opioid doses. There was, however, a paucity of trials directly answering this question and low-quality evidence limits the conclusions that can be drawn. It is clear that further high-quality clinical trials are needed to answer this question and to guide clinical practice.