BackgroundChronic pain is commonly treated with analgesic medication. Non-adherence to prescribed pain medication is very common and may result in sub-optimal treatment outcome. The aim of this review was to investigate the prevalence of medication non-adherence and to present determinants that may help identify patients at risk for non-adherence to analgesic medication. MethodsA search was performed in PubMed and Embase with systematic approach including PRISMA recommendations. Individual risk of bias was assessed and systematic data extraction was performed. ResultsTwenty-five studies were included. Non-adherence rates to pain prescriptions ranged from 8% to 62% with a weighted mean of 40%. Underuse of pain medication was more common than overuse in most studies. Factors that were commonly positively associated with non-adherence were dosing frequency, polymedication, pain intensity, and concerns about pain medication. Factors negatively associated with non-adherence were age, again pain intensity and quality of the patient-caregiver relationship. Underuse was positively associated with active coping strategies and self-medication, and negatively associated with perceived need for analgesic medication. Overuse was positively associated with perceived need, pain intensity, opioid use, number of prescribed analgesics, a history of drug abuse, and smoking. ConclusionNon-adherence to analgesic medication use is very common in the chronic pain population. The choice for pharmacological therapy should not only be based upon pain diagnosis but should also take the risks of non-adherence into account. The value of adherence monitoring or adherence enhancing interventions has to be investigated in future studies.