The German Society for the Study of Pain (DGSS) commissioned a meta-analytic review of the evidence on the long-term effects of opioids, non-opioid analgesics and cognitive- behavioral procedures for chronic non-cancer pain. A multidisciplinary expert panel was established to review the evidence and formulate recommendations as far as possible on the basis of means, standard deviations and group sizes from randomized controlled trials. Effect size estimates of analgesic effects (SMDs, WMDs) from studies were below clinical significance, whenever the reported data permitted evaluation and nearly equal for all the investigated medical therapies and pain syndromes. Therefore, the LONTS guidelines focus on the prevention of adverse effects and misuse and a multidisciplinary approach for the treatment of chronic pain is strongly recommended. Principles of opioid prescription and on the management of risks associated with the long-term use of opioids are described.