Introduction:To conduct a literature review exploring the humanistic burden, costs, and guideline recommendations for non-surgical management of moderate-severe pain in knee osteoarthritis (KOA). Methods: Published studies (2018-25 April 2023) assessing the burden of moderate-severe pain in KOA were identified by searching Medline, Embase, EconLit, and Cochrane database, supplemented with grey literature hand searches and reference list snowballing. Treatment guidelines were also identified for key countries. Results: This review included 106 publications and 37 treatment guidelines. Patients with moderate-severe pain were found to experience a low quality of life (QoL) and an impaired ability to perform daily tasks. The economic burden of KOA was substantial, including cost of medical