Osteochondral (OC) tissue is a mechanically graded structure that enables efficient load transmission across the joint. Its integrity is maintained through mechanobiological processes in which cells sense and respond to external forces via mechanotransduction pathways. Chondrocytes in cartilage, for example, detect compressive and shear stresses through integrins, ion channels, and cytoskeletal rearrangements, leading to changes in extracellular matrix (ECM) synthesis and turnover. Similarly, osteocytes within subchondral bone act as primary mechanosensors, converting fluid shear stresses in the lacunocanalicular network into biochemical signals that regulate osteoblast and osteoclast activity through different cell signaling pathways. Disruption of these finely tuned signaling mechanisms—whether by aging, injury, or disease—alters tissue homeostasis and contributes to the development of degenerative joint disorders such as osteoarthritis. In this chapter, it will be analyzed mechanobiology at the tissue and cellular levels, evaluated how tissue engineering strategies have sought to exploit mechanotransduction to enhance osteochondral repair, and considered how the interplay between biomechanics, cellular signaling, and inflammation can inform the design of future regenerative therapies.