Osteoarthritis is a major public health issue due to its impact in term of handicap. Moreover, ageing of the world population and outbreak of obesity in industrialized and non-industrialized countries will dramatically increase its incidence in the next years. Regarded as a multi-factorial disease, today mechanistic and inflammatory theories are no more opposed but, on the contrary, are framed within the same continuum: osteoarthritis, inflammation and degeneration. In order to collect major information in a benchmark book on the fundamental aspects of this disease, internationally well-known authors, from multiple specialties, gathered to analyze, dissect and finally try to understand the secrets of a disease which should no more be regarded as the common and relentless result of ageing or of passive wear but much more as an active disease able to benefit from the best targeted pharmacological (anti-cytokines, inhibitors of signaling pathways, inhibitors of proteases, etc.) and non-pharmacological (cellular therapy, gene therapy, cartilage engineering etc.) therapies, current and future.