Background: In combination with non-pharmacological interventions, opioids may safely reduce chronic breathlessness in patients with severe illness. However, implementation in clinical practice varies. Aim: To synthesise the published literature regarding health professionals���, patients��� and families��� views on the use of opioids for chronic breathlessness, identifying issues which influence implementation in clinical practice. Design: Systematic review and synthesis using the five-stage framework synthesis method. Data sources: Three electronic databases (MEDLINE, Embase via OVID, ASSIA via Proquest) were searched (March 2020) using a predefined search strategy. Studies were also citation chained from key papers. Papers were screened against a priori eligibility criteria. Data were extracted from included studies using the framework synthesis method. Qualitative and quantitative data were synthesised using the pillar process. Included studies were critically appraised using the Mixed-Methods Appraisal Tool. Results: After de-duplication, 843 papers were identified. Following screening, 22 studies were included. Five themes were developed: (i) clinician/patient characteristics, (ii) education/knowledge/experience, (iii) relationship between clinician/family, (iv) clinician/patient fear of opioids and (v) regulatory issues. Conclusions: There are significant barriers and enablers to the use of opioids for the symptomatic reduction of chronic breathlessness based on the knowledge, views and attitudes of clinicians, patients and families. Clinicians��� interactions with patients and their families strongly influences adherence with opioid treatment regimens for chronic breathlessness. Clinicians���, patients��� and families��� knowledge about the delicate balance between benefits and risks is generally poor. Education for all, but particularly clinicians, is likely to be a necessary (but insufficient) factor for improving implementation in practice.