In recent years the argument that enthesitis is the primary lesion in many or most patients with psoriatic arthritis and spondyloarthritis has gained further credence from animal models including IL23/IL17 axis and TNF dependent models. The role of joint biomechanics at entheses and other sites of high physical stressing as a unifying underlying basis has also been strongly supported by animal models. Mirroring the animal model data, it has been empirically shown that therapies that work for entheseal-related inflammation in man including IL23/17 axis or TNF cytokine antagonism are effective for entheseal pathology. The biological basis for the effectiveness of other therapies including PDE4 inhibitors on enthesitis is poorly understood due to the relative difficultly in procurement of entheseal tissue. This absence of a histological gold standard renders it difficult to decipher how effective various therapies are in treatment of enthesitis. Despite advances in understanding enthesitis in animal models, there is a dearth of data thus far on the immunology of human entheses that likely will be key to further refinements in therapy development.