Many of the important questions for those who prescribe opioids in chronic pain, and important for those who take the drugs, still have to be answered with inadequate evidence, because we lack randomised trials on these topics. Two of the principal reasons for "failure' of opioids to relieve pain, incident pain and neuropathic pain, are discussed. Some specific adverse effect problems are addressed, and the paper concludes with a section on the vexed issue of opioid prescription in non-cancer pain.