Chronic pain disorder is widely understood as a "biopsychosocial" phenomenon, meaning that it is influenced by psychology and certain life events. This broad understanding of chronic pain suggests that central responses during pain experience should be altered in patients compared with pain-free volunteers. A total of 34 studies are reviewed, revealing a widespread "neuromatrix" of activated regions. These regions include the brain stem, thalamus, and lentiform nucleus, and the insula, prefrontal, parietal, and anterior cingulate cortices. Meta-analysis of these studies does not reveal any single region or pattern of activity to be of particular influence during chronic pain but does reveal a generally reduced response to noxious stimulation in patients with concomitant clinical pain. The relevance of this finding remains unclear with the most parsimonious explanation being increased response variability in patients. More specific findings can be revealed when using a hypothesis-generated approach; further investigation of genetic and developmental predisposition is suggested.