Chondrocytes, which are the only cell type in the articular cartilage, show substantial morphological and functional differences, depending on their location within the tissue. In OA cartilage, outstanding modifications have been reported concerning their structure and functions. Based on the principle that both structure and function run in a parallel manner, new concepts are arising related to morphological observations. Observations on OA chondrocytes, such as cytoskeleton disruption, development of the secretory machinery (rough endoplasmic reticulum and Golgi complex), and cell death by apoptosis, among others, certainly must be related to the role of chondrocytes in OA pathogenesis. In this degradative process, it has been acknowledged that cell death, matrix degradation and subchondral bone remodelling are the main causes of cartilage breakdown in osteoarthritis. The aim of this review was to correlate and integrate in a logical manner the modifications of chondrocytes with cartilage breakdown during osteoarthritis pathogenesis. Furthermore, we intend to open a debate on cell cycle and mitosis, as well as on signalling molecules that might be involved in the morphofunctional changes in OA chondrocytes, which we propose to name "activation" and "transdifferentiation" of chondrocytes. We expect this analysis to be useful for studying OA pathogenesis in depth, with the aim of finding new strategies for the early diagnosis and therapeutic procedures for this invalidating disease, which is already an important public health problem.