Parenteral opioids are commonly used for labor pain relief and have been the subject of research for many years. The objectives of this review were to determine the safety and effectiveness of parenteral opioids in this context. Of 85 trials systematically reviewed, 48 comprising more than 9800 were included, but the number of trials contributing data to individual outcome measures is very limited. Epidural provides better pain relief. However, if women opt for systemic analgesia, no strong preference for any of the opioids can be recommended. Pethidine is the most commonly used opioid worldwide, and although there are considerable doubts about its analgesic effectiveness and concerns about its potential maternal, fetal, and neonatal side effects, it has the virtue of familiarity and low cost. There is as yet no convincing research evidence to show that alternative opioids are better. In view of the large number of women who receive opioids in labor and the paucity of research evidence about the relative effectiveness and side effects of different opioids and opioids compared with other methods (apart from epidural), well-designed and suitably sized trials of pethidine versus the main alternatives that address substantive outcomes for mothers and babies are strongly recommended.