Pain has often been regarded merely as a symptom that serves as a passive warning signal of an underlying disease process. Using this model, the goal of treatment has been to identify and address the pathology causing pain in the expectation that this would lead to its resolution. However, there is accumulating evidence to indicate that persistent pain cannot be regarded as a passive symptom. Continuing nociceptive inputs result in a multitude of consequences that impact on the individual, ranging from changes in receptor function to mood dysfunction, inappropriate cognitions, and social disruption. These changes that occur as a consequence of continuing nociceptive inputs argue for the consideration of persistent pain as a disease entity in its own right. As with any disease, the extent of these changes is largely determined by the internal and external environments in which they occur. Thus genetic, psychological and social factors may all contribute to the perception and expression of persistent pain. Optimal outcomes in the management of persistent pain may be achieved not simply by attempting to remove the cause of the pain, but by addressing both the consequences and contributors that together comprise the disease of persistent pain.