Current treatments for TMDs lack long-term efficacy and are palliative, motivating tissue-engineering for repair or replacement of the injured or ailing tissues in the TMJ, such as the disc. Scaffold-based or scaffold-free approaches, cell sources, biochemical stimuli, and mechanical stimuli are all elements of the tissue-engineering process that need to be considered to tailor TMJ disc construct properties. Large animals can serve as models of human TMDs orthotopic implantation in large animal models is a necessary translational step.