OBJECTIVES: Opioid use disorder (OUD) is characterised by repeated, compulsive seeking or use of an opioid, despite adverse social, psychological and/or physical consequences. Patients with OUD have a variety of symptoms and a reduced health-related quality-of-life (HRQoL). We performed a comprehensive literature review that included an evaluation of the types of instruments used to assess severity of patient symptoms and the impact of OUD on HRQoL. METHODS: A structured, comprehensive literature review was conducted to identify articles describing the humanistic (symptoms/caregiver) burden of OUD. Global literature databases, guideline databases, regulatory and health technology assessment agency websites, and relevant society guidelines were searched. Searches were conducted for articles published between 2000–2015. Articles were not restricted by language. Eligible articles were those reporting on OUD (including opioid abuse and dependence) and providing data on at least one topic of interest. RESULTS: A total of 2,234 records were screened, of which 202 articles met the selection criteria and were included in this literature review. Of these, 45 articles reported on a humanistic burden of OUD, within which 54 instruments were identified. These included: general HRQoL instruments (17), instruments for mental health assessment (9), specific instruments for drug abuse (13) and questionnaires on relationships and social support (15). Most instruments were reported only once, with 5 instruments (WHOQOL-BREF, SF-36, SF-12, Opiate Treatment Index and Addiction Severity Index) reported in ≥4 articles each. None of the instruments were specifically developed for OUD. CONCLUSIONS: Our review indicates a wide range of instruments are used to assess the humanistic burden in OUD. However, compared with patient symptoms, HRQoL was assessed less often and only using general instruments. Our findings suggest an unmet need for the development of OUD disease-specific HRQoL instruments that can effectively assess the different dimensions of the humanistic burden associated with this chronic relapsing disease.