Cartilage is the soft tissue covering the long bones of articulating joints inthe human body. This remarkable tissue can withstand repeated cycles of loading over decades of a person’s life. However, with normal and excess use, natural aging, disease, and trauma the tissue experiences degeneration eventually leading to inferior mechanical properties. The deterioration of the joint function can lead to osteoarthritis, which is one of the most common forms of degeneration of cartilage and affects more than 27 million people in the United States alone. Although there is a high occurrence of disease and degeneration, current treatment options for cartilage repair do not tackle the underlying cause of deterioration of the tissue. Cartilage has a variety of functions such as dissipating loads and providing mechanical support. These functions require different structural, compositional and mechanical properties. Thus, the overall goal of this dissertation was to investigate the relationship between structure, composition, and microscale mechanics and their relevance to disease and degeneration. Studies in cartilage have been mainly focused on articular hyaline cartilage and with the recent advances in experimental techniques, high quality measurements of the distinct local properties of the tissue have been made. However, there is still a need for understanding a particular type of tissue, which is heavily understudied, namely the temporomandibular joint cartilage (TMJ). The temporomandibular joint cartilage is located in between the fossa eminence complex and the mandibular condyle of the jaw. This unique tissue differentiates from articular hyaline cartilage by having a highly aligned fibrous surface layer. Furthermore, TMJ cartilage has distinct depth dependent properties that allow it to withstand extended periods of load. In order to understand the fundamental properties of TMJ cartilage, the relationship between structure, composition, and microscale shear mechanics in porcine, canine, and human TMJ cartilage was investigated (Chapter 2). Furthermore, to investigate the effect of disease and degeneration in TMJ cartilage, age related changes due to collagen crosslinking and its effect to the local shear mechanics were examined (Chapter 3). Lastly, the role of viscosupplementation affecting the joint stress environment and its efficacy in cartilage repair in an in-vivo rabbit osteochondral (OCL) defect model was evaluated (Chapter 4). Overall, this dissertation demonstrates that TMJ cartilage has distinct mechanical properties varied by structural zones and compositional changes which yielded high gradients in modulus (Chapter 2). Furthermore, the effect of collagen crosslinking in native and artificially ’aged’ TMJ cartilage implicated how natural aging and altercation of the extracellular matrix in a laboratory setting could be different (Chapter 3). Lastly, a single delayed injection of recombinant human lubricin in an in-vivo rabbit OCL defect model showed that lubricin does not inhibit cartilage repair and in some aspects vastly improves the quality of repair (Chapter 4).