The last decade (between 2000 and 2010) was designated as the Bone and Joint Decade by the UN and the WHO to raise public awareness of the ever-growing burden of musculoskeletal and locomotion disorders on society. One of the tissues involved is cartilage–the most unique type of connective tissue in the body. Calcium homeostasis and poly(ADP-ribose) polymerase (PARP) dependent pathways represent two important aspects of in vitro chondrogenesis. Calcium, the most ubiquitous signalling factor, regulates many aspects of cartilage differentiation. As cartilage is an avascular tissue characterised by low oxygen tension, chondrocytes have to maintain their function in hypoxia, and they frequently encounter reactive oxygen species (ROS)–PARP is the enzyme that eliminates the detrimental effects of ROS. This book summarises the newest results of research into these processes in chondrifying mesenchymal high density cell cultures. This work should be useful for professionals or students who are interested in signaling pathways that regulate the formation of cartilage under normal and pathological conditions.