Tendon tissue plays a central role in force transmission from skeletal muscles to bones and is subject to a considerable amount of overuse injuries associated with occupation and leisure exercise. It has been shown that connective tissue within and around tendon displays increased blood flow and metabolic activity during exercise in vivo and that the extracellular matrix is stimulated by physical activity whereby both collagen synthesis and degradation are enhanced in both tendon and muscle. Training leads to a net synthesis of collagen type I in tendon, and the thicker tendons that well-trained individuals possess contribute to a lower relative loading of the tendons during exercise. Signals for increased collagen synthesis seem to run in parallel with mechanically induced activation of protease driven degradation of connective tissue in tendon and muscle. Hormonal growth factors as well as inflammatory mediators play a role for this effect, but the relative importance of individual factors in the development of acute or chronic tendon injuries in relation to sports remains uncertain. Newly developed in-vivo techniques open new possibilities for a deeper understanding of the pathogenesis behind tendon overuse injuries.