The management of patients with chronic pain is a common clinical challenge. Indeed, chronic pain is often inadequately controlled in patients with cancer and in those with non-cancer chronic pain. Because of the complex nature of chronic pain, successful long-term treatment is more difficult than for acute pain. Most often acute pain is nociceptive, whereas chronic pain can be nociceptive (i.e., in response to noxious stimuli), neuropathic (i.e., initiated by a primary lesion or dysfunction in the nervous system) or mixed in origin. Opioids are the current standard of care for the treatment of moderate or severe nociceptive pain. Opioids mediate their actions by binding and activating receptors both in the peripheral nervous system and those that are found in inhibitory pain circuits that descend from the midbrain to the spinal cord dorsal horn. Opioid agonists exert a number of physiological responses including analgesia, which increases with increasing doses. The use of opioids to manage pain in patients with cancer is well accepted. The WHO step-wise algorithm for analgesic therapy based on pain severity reserves the use of opioid therapy for moderate and severe pain. The WHO algorithm has proven to be highly effective for the management of cancer pain. However, the use of opioids to treat patients with chronic non-cancer pain is controversial because of concerns about efficacy and safety, and the possibility of addiction or abuse. The results of clinical surveys and retrospective case series involving patients with non-cancer chronic pain have been inconsistent in regard to resolving these controversial issues. The oral route of drug administration is most appropriate for patients receiving opioids; although rectal, transdermal and parenteral routes of administration are used in specific situations. For continuous chronic pain, opioids should be administered around-the-clock and several long-acting formulations are available that require administration only once or twice daily. Opioid doses should be titrated according to agent-specific schedules to maximise pain relief and maintain tolerability. Adverse effects include constipation, nausea and vomiting, sedation, cognitive impairment and respiratory depression. Tolerance to the analgesic and adverse effects as well as physical dependence, which causes withdrawal symptoms upon discontinuance, may occur with opioid use. Estimates of addiction rates among patients with chronic non-cancer pain range from 3.2 to 18.9%. Successful pain treatment and symptom management is an attainable goal for the majority of patients with chronic pain. Further controlled clinical trials are needed to define the role of opioid therapy in chronic non-cancer pain, and to establish criteria for patient selection and specific treatment algorithms.