Clinical pain is multifactorial. It is not simply the consequences of a “switching on” of the pain system in the periphery, but also excitability of central nociceptive areas. For pain management to be successful in treating the upper extremity both the peripheral and central symptoms must be targeted. The patient education process must ensure that patients understand their symptoms and treatment program. This article discusses recent advancements in the neuroscience of pain that impact evolving strategies to identify and treat the pain mechanisms.