Studies of recent years on human tendinopathies have provided us with evidence of a local, non-neuronal production in tendon cells (tenocytes) of signal substances traditionally confined to neurons. These substances include acetylcholine, catecholamines, substance P, and glutamate. Furthermore, the receptors for several of these substances have been found on nerve fascicles and in blood vessel walls, as well as on the tenocytes themselves, of the tendon tissue. The findings provide the basis for locally produced signal substances to influence pain signaling, vascular regulation, and/or tissue changes in tendinopathy. This reinforces a previously presented “biochemical” hypothesis for tendinopathy, suggesting that biochemical mediators in the tendon tissue might influence/irritate nociceptors, in or around the tendon, to cause chronic tendon pain. The potential clinical implications of the studies are considerable.