Osteoarthritis is a chronic degenerative disorder that currently represents one of the main causes of disability within the elderly population and an important presenting complaint overall. The pathophysiologic basis of osteoarthritis entails a complex group of interactions among biochemical and mechanical factors that have been better characterized in light of a recent spike in research on the subject. This has led to an ongoing search for ideal therapeutic management schemes for these patients, where glucosamine is one of the most frequently used alternatives worldwide due to their chondroprotective properties and their long-term effects. Its use in the treatment of osteoarthritis is well established; yet despite being considered effective by many research groups, controversy surrounds their true effectiveness. This situation stems from several methodological aspects which hinder appropriate data analysis and comparison in this context, particularly regarding objectives and target variables. Similar difficulties surround the assessment of the potential ability of glucosamine formulations to alter glucose metabolism. Nevertheless, evidence supporting diabetogenesis by glucosamine remains scarce in humans, and to date, this association should be considered only a theoretical possibility.