BACKGROUND: The knee is the largest synovial joint in the body and is a common cause of lower-limb disability in patients over the age of 60. One of the most common ailments affecting the knee is osteoarthritis, an inflammatory process that leads to pain and altered joint function. Osteoarthritis (OA) of the knee affects a large number of Americans and is a common cause of disability in older adults. The prevalence of arthritis in the U.S. is high with 29.3% of persons aged 45-64 and 49.6% of persons over 65 reporting a doctor-diagnosed arthritis. It is estimated that by the year 2030, the number of people over 65 with osteoarthritis will reach more than 70 billion. This high prevalence combined with the potential of knee osteoarthritis to lead to permanent disability places a large burden on the healthcare system. Osteoarthritis was once thought of as a “wear and tear” process but over the years, medical research has shown that the pathogenesis of OA is multifactorial and includes biomechanical factors, proinflammatory mediators, and proteases. Progressive destruction of joint cartilage in regions prone to maximal joint loading, leads to an increase in chondrocyte activity. Chondrocytes maintain joint cartilage through a variety of anabolic and catabolic activities. The upregulation of chondrocyte activity leads to an increase in the production of proinflammatory cytokines and proteases, which ultimately leads to matrix degradation. Damage to the extracellular matrix leads to cartilage loss and OA symptoms including pain, swelling, grinding, catching and locking, all of which are suggestive of internal derangement of the knee caused by cartilage damage and bony fragments. Sclerosis of the bone, osteophyte formation, and synovial inflammation are also important characteristics of OA. OA of the knee is classified based on its etiology as either primary or secondary. Primary knee OA is idiopathic meaning there is no known cause while secondary knee OA can result from previous surgery, previous trauma, congenital malformations, or even metabolic (ex: Rickets, chondrocalcinosis, etc.) or endocrine (ex: hyperparathyroidism, acromegaly, etc.) disorders. Modern advances in healthcare are allowing patients to live longer and as a result, the number of patients suffering from osteoarthritis will only continue to increase. As the number or patients suffering from OA increases, so will the burden on physicians and advanced practice providers (APPs) to care for these patients. Therefore, physicians and APPs should make themselves aware of the various modalities that are available to patients to help them manage their symptoms. While one approach or modality might work for one patient, it may not work for the next and so it is vital that we offer each patient an individualized treatment plan. Treatment plans should focus on each patient’s current symptoms, their normal activity level, and the outcomes they hope to achieve. Patient-centered outcomes include decreased pain, fewer limitations in their daily life, and less morning stiffness. The definitive treatment of knee OA is total knee arthroplasty (TKA) or total joint replacement. TKA is indicated only in patients with advanced OA when conservative treatment has been tried without success. The purpose of this paper is to discuss the non-surgical management of knee OA and to compare stem cell injections vs. platelet-rich plasma injections to corticosteroid or hyaluronic acid injections in decreasing pain and improving function in patients over the age of 60 with knee osteoarthritis.