 Chondrocyte are the main cell type in articular cartilage, and they are embedded in an avascular, specialized extracellular matrix, ECM, composed of collagen, proteoglycans, and non-collagen proteins. These cells are responsible for the synthesis and turnover of the ECM, and they play important roles in the regulation of cell phenotype through crosstalk with the ECM. Chondrocyte live in an anaerobic environment with a low oxygen supply, but they require oxygen for some of their metabolic processes. Oxygen is supplied by the synovial fluid, and this review focuses on the transcriptional and signaling mechanisms involved in chondrocyte differentiation, homeostasis, senescence, and cell death. Additionally, the effects of chondrocyte sulfate and other molecules as anti-inflammatory agents are discussed. This article was authored by Yara M. Michael Aksai, Raquel Y. A. Bakurin, and Nubia N. P. Rodriguez.