The role of opioid therapy in chronic musculoskeletal disease continues to be controversial. However, recent years have seen a gradual shift towards the use of opioid therapy in chronic non-malignant pain (CNMP) following recognition that at least a subpopulation of such patients appears to benefit from long-term opioid treatment. Misconceptions about opioids and the associated risk of dependence stemmed from older research that was fundamentally flawed. More recent, rigorous research has yielded clearer statistics on opioid dependence and has highlighted the need for screening to identify individuals who may require closer monitoring during long-term opioid therapy. Controlled-release formulations (oral and transdermal) for the management of steady pain, in conjunction with fast-acting, immediate-release formulations for the management of breakthrough pain, may be available for a wide range of opioid analgesics, providing comprehensive therapy systems for use in CNMP. However, there are no universal criteria that can be confidently used to select CNMP patients who might profit from or be responsive to opioid therapy. Opioid treatment must therefore be individualised for each patient, based on a clear understanding of drug absorption, metabolism, toxicity and binding characteristics, using opioid switching strategies where appropriate. Practical guidelines for opioid therapy in CNMP include regular and systematic checks of treatment results to adjust therapy for each individual patient and to ensure optimum benefit.