This chapter addresses various aspects of pain and pain inhibition. Inhibitory mechanisms are explained and therapeutic implications are discussed. The stress response is considered, as the orientation of the autonomic nervous system influences the choice of therapeutic intervention. Only if the treating therapist possesses a basic understanding of this subject can they credibly and appropriately convey it to their patients. The majority of our patients come to us because of pain. We know that information about their main problem is of utmost importance to patients. This is especially true for patients with chronic pain. We also know that information, when delivered as is commonly done focusing on anatomical and biomechanical aspects, is of rather limited effectiveness. This type of information is nowadays associated with the development of fear behaviors, catastrophizing, and misconceptions about the underlying problem of pain. Therefore, the so-called pain neuroscience education is also addressed.