Osteoarthritis (OA) is a leading cause of disability in the United States. Current treatment focuses on symptom relief and improving a patient's overall function. Pharmacological treatments aim to correct symptomatic complaints as well as structural problems in OA. Glucosamine (sulfate or hydrochloride) and chondroitin sulfate have been linked as an optional treatment in OA for several years. There is controversy, however, surrounding their use and efficacy. The American Academy of Orthopaedic Surgeons published clinical practice guidelines in 2008 that recommended against the use of glucosamine and chondroitin sulfate (p. ii). Despite conflicting results on the degree of efficacy, the most current research suggested that glucosamine and chondroitin sulfate have the potential to provide pain-relieving benefits as well as possibly decrease the effects of joint space narrowing. The purpose of this article was to document the most current research evidence on the use and efficacy of glucosamine and chondroitin sulfate supplements for patients with symptomatic OA of the knee as well as create an evidence-based, best practice educational tool describing a treatment algorithm for nurse practitioners treating a patient with symptomatic OA of the knee.