Since modern brain imaging of pain began 20 years ago, networks in the brain related to pain processing and those related to different types of pain modulation, including placebo, have been identified. Functional and anatomical connectivity of these circuits has begun to be analyzed. Imaging in patients suggests that chronic pain is associated with altered function and structural abnormalities in pain modulatory circuits. Moreover, biochemical alterations associated with chronic pain are being identified that provide information on cellular correlates as well as potential mechanisms of structural changes. Data from these brain imaging studies reinforce the idea that chronic pain leads to brain changes that could have functional significance.