Description: Knee osteoarthritis is a degenerative disease that causes disability and persistent pain. Currently, treatment modalities for osteoarthritis focus on pain reduction and symptom management, but do little to address disease modification. Presently, the treatment of choice for knee osteoarthritis is total knee replacement surgery. Total knee replacement surgery carries significant risks and does not guarantee improvement in joint pain or function. In the last decade, advances in regenerative medicine have proposed the use of mesenchymal stem cells as a treatment strategy for joint preservation, cartilage regeneration and improved joint function in patients with osteoarthritis. The aim of this integrative literature review was to explore the use of mesenchymal stem cells as a treatment modality for the management of knee osteoarthritis and to analyze the safety and effectiveness of the intervention. An extensive search of the academic databases Cumulative Index of Nursing and Allied Health Literature (CINAHL), and PubMed was conducted using the search terms, mesenchymal stem cells and knee osteoarthritis. The findings of this literature review indicate regenerative medicine has the potential to be an effective alternative to knee replacement surgery. Furthermore, the review provides significant evidence that the use of mesenchymal stem cells for the treatment of knee osteoarthritis is safe and effective; however, more research and clinical trials are needed before its use can become standard practice.