Osteo-articular diseases affect many elderly people, resulting in worse quality of life and a substantial public health cost. Osteoarthritis, inflammatory articular diseases and conditions associated with cartilage disruption are the most frequently diagnosed. Non-steroidal anti-inflammatory drugs, glucocorticoids and physiotherapy are used to treat affected patients, while some nutraceutical products containing chondroprotective and osteotropic substances have been shown to improve their signs and symptoms. However, the true absorption and efficacy of these substances in humans is largely unknown. The absorption of hyaluronans and chondroitin sulfate is likely negatively affected by their high molecular weight. Nevertheless, many published papers have reported significant improvements in symptoms and articular functionality in patients taking these compounds. This paper attempts to clarify the apparent dichotomy between absorption and efficacy, and compare the clinical evidence for the bioavailability of hyaluronic acid with that of its precursor N-acetyl glucosamine.