The tendon-to-bone insertion site (enthesis) represents a fascinating example of a multiscale natural optimization of the joint between composite orthotropic (tendon) and composite isotropic (bone) tissues with vastly different properties. The composition and properties of tendon vary in a narrow region adjacent to bone. The result is an optimized attachment possessing desirable strength, stiffness and toughness. The multifunctional optimization is achieved through material and morphological grading occurring on nanoscale, microscale and macroscale. The effectiveness and response of the enthesis are affected by its mechanics on all these scales. In this paper, we outline mechanical issues pertinent to multiscale mechanics of enthesis concentrating on state-of-the art knowledge as well as pressing issues that should be addressed to properly and accurately model enthesis. We demonstrate aspects of mechanics on several scales that contribute to an optimized insertion site. In case of a post-trauma healing, recovered insertion site does not exhibit such optimization as is reflected in high repeated failure rates that can reach up to 94% in certain populations. Therefore, the multiscale mechanical analysis of the tendon-to-bone insertion site can help in developing restorative surgical protocols and postoperational therapy. Such knowledge is also helpful for biomimetic engineering solutions aimed at joining of dissimilar materials.