Tendons transmit power from muscles to bones, and ligaments maintain the stability of joints, thus producing smooth and flexible movements of articular joints. However, tendons have poor self-healing ability upon damage due to injuries, diseases, or aging. To maintain homeostasis or promote regeneration of the tendon/ligament, it is critical to understand the mechanism responsible for the coordination of tendon/ligament-specific gene expression and subsequent cell differentiation. In this review, we have discussed the core molecular mechanisms involved in the development and homeostasis of tendons and ligaments, with particular focus on transcription factors, signaling, and mechanical stress.