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Background: The second scheduled update of the German S3 guidelines on long-term opioid therapy for chronic noncancer pain (CNCP), the LONTS (AWMF registration number 145/003), was started in December 2018., Methods: The guidelines were developed by 28 scientific societies and 2 patient self-help organizations under the coordination of the German Pain Society. A systematic literature search in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Scopus databases (up until December 2018) was performed. The systematic reviews with meta-analyses of randomized controlled trials with opioids for CNCP from the previous versions of the guideline were updated. Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine. The strength of the recommendations was established by formal multistep procedures in order to reach a consensus according to the Association of the Medical Scientific Societies in Germany (AWMF) regulations. The guidelines were reviewed by four external pain physicians. Public comments were possible for 4 weeks., Results: Opioid-based analgesics are a drug-based treatment option for short-term (4-12 weeks), intermediate-term (13-25 weeks) and long-term (≥26 weeks) therapy of chronic osteoarthritis, diabetic polyneuropathy, postherpetic neuralgia and low back pain. Contraindications are primary headaches as well as functional somatic syndromes and mental disorders with the (cardinal) symptom pain. Based on a clinical consensus the guidelines list other medical conditions for which a therapy with opioids can be considered on an individual basis. Long-term therapy of CNCP with opioids is associated with relevant risks., Conclusion: A responsible administration of opioids requires consideration of possible indications and contraindications as well as regular assessment of efficacy and adverse effects. Opioids remain a treatment option for CNCP if nonpharmacological therapies are not effective and/or other drugs are not effective, are not tolerated or are contraindicated.