Osteoarthritis (OA) is a disease of high ethical and economical importance. In advanced stages, the patients suffer from severe pain and restriction of mobility. The consequence in many cases is an inability to work and often the substitution of the diseased joint with an artificial implant becomes inevitable. As cartilage tissue itself has only very limited capacities of self-renewing, the development of this disorder is chronic and progressive. Generally, OA is diagnosed in more advanced stages, when clinical and radiographic signs become evident. At this time point the options for therapeutic intervention without surgery are limited. It is, therefore, crucial to know about the basic incidents in the course of OA and especially in early stages to develop new diagnostic and therapeutic strategies. Numerous studies on human osteoarthritic tissue and in animal models have addressed various aspects of OA progression to get a better understanding of the pathophysiology of this disease. This review presents an overview on different aspects of OA research and the cellular and molecular alterations in degenerating cartilage.