Knee osteoarthritis is the most common form of arthritis. Given the aging of the world's population, the burden of this disease is expected to increase significantly over the next few decades. As a pharmacological agent, glucosamine has been investigated for the treatment of symptoms and progression of knee osteoarthritis, demonstrating symptomatic and disease-modifying effects. However, among the glucosamine studies conducted to date in knee osteoarthritis, there have been conflicting results due to differences and/or weaknesses in study design and sample size, in addition to product formulation, salt and quality. This review describes the current knowledge regarding the pharmacokinetics of glucosamine to provide a means for the interpretation of the pharmacodynamic and clinical efficacy results obtained in the different clinical trials.