This article introduces the scientific basis for the understanding of pain mechanisms and highlights the importance of endogenous excitatory and inhibitory controls in the central nervous system. These innate control systems have an impact on the evolution of chronic pain and may be manipulated to alter the pain process, and therefore have implications regarding treatment. Understanding neurophysiologic mechanisms involved in the development and maintenance of pain can help the clinician to devise a more effective treatment plan guided by pathophysiologic dysfunction. Keeping in mind the heterogeneity of the pain response and the unique characteristics of an individual patient will lead to better patient care.