Osteoarthritis (OA), the most common form of arthritis, is generally characterized by a slowly progressive degeneration of articular cartilage, particularly in the weight-bearing joints. It has a stronger prevalence in women, and its incidence increases with age. OA is a major and growing health concern in developed countries, owing to steadily increasing life expectancy and the demand for better quality of life. Because of its chronic nature and nonfatal outcome, OA affects the growing population of the elderly over an increasing time span. Moreover, despite its relatively benign character, OA is one of the most disabling diseases; it is responsible for increasing financial and social burdens in terms of medical treatments, forced inactivity, loss of mobility, and dependence. Despite a growing awareness of OA as a medical problem that has yet to reach its maximum impact on society, there is a surprising absence of effective medical treatments beyond pain control and surgery. So far, only symptom-modifying drugs are available, while there remains a major demand for disease-modifying treatments of proven clinical efficacy. This demand will hopefully be met in the future by some of the drugs that have been pressed into development and are now at different stages of clinical investigation. Nevertheless, the current lack of effective treatments reflects a still insufficient knowledge of cartilage with respect to its metabolism, interactions with other joint tissues, and causes and mechanisms (possibly of very different nature) leading to failure of its turnover.