Peripheral inflammation or nerve damage result in changes in nervous system function, and may be a source of chronic pain. A number of animal studies have indicated that central neural plasticity, including sensitization of neurons within the spinal cord and brain, is part of the response to nervous system insult, and can result in the appearance of altered sensation, including pain. It cannot be assumed, however, that data obtained from animal models unambiguously reflects CNS changes that occur in humans. Currently, the only noninvasive approach to determining objective changes in neural processing and responsiveness within the CNS in humans is the use of functional imaging techniques. It is now possible to use functional magnetic resonance imaging (fMRI) to measure CNS activation in the trigeminal ganglion, spinal trigeminal nucleus, the thalamus, and the somatosensory cortex in healthy volunteers, in a surrogate model of hyperalgesia, and in patients with trigeminal pain. By offering a window into the temporal and functional changes that occur in the damaged nervous system in humans, fMRI can provide both insight into the mechanisms of normal and pathological pain and, potentially, an objective method for measuring altered sensation. These advances are likely to contribute greatly to the diagnosis and treatment of clinical pain conditions affecting the trigeminal system (e.g., neuropathic pain, migraine).