The overall turnover of the tendon in humans seems to be taking primarily within the first 17 years of life, indicating that the basic structure remains relatively unchanged through adult life. Nevertheless, mechanical loading of adult human tendon results in an up-regulation of collagen synthesis and collagen degradation relatively independent upon tendon loading intensity, and indicates a “fine-tuning” of e.g. cross link formation in relation to level of physical activity and accompanies the relatively fast change in tendon mechanical properties with either training or immobilization. Development of tendinopathy is suggested to be coupled to a mismatch between loading and adaptation, and results in pain, palpatory soreness, tendon thickening, rounded cells, disorganized matrix and GAG accumulation, plus angiogenesis. The best documented treatment is controlled strength training exercises, and other treatments have either good but short lasting effect, or minimal to no effect upon the tendinopathy. Although we today have a better grasp on the different theories behind development of tendinopathy, there are still many challenges, such as a mismatch between symptoms and imaging findings (e.g. flow), a mismatch between tissue pathology and perceived pain, and a mismatch between general tendon tissue changes and specific regional presentations, differential locations and variation in patient characteristics.