Since the discovery in the early 1990s that magnetic resonance imaging (MRI) can be used for functional imaging of the human brain, the technique has been used to examine the contribution of thalamic and cortical areas to the human pain experience. In a series of studies in this laboratory, functional MRI (fMRI) of noxious heat-, cold-, and median nerve stimulation-evoked activations demonstrated the involvement of the thalamus and multiple cortical areas in pain. The cortical areas identified included the primary and secondary somatosensory cortex (S1, S2), the anterior insula and the anterior cingulate cortex. The data also revealed a significant intersubject variability in the activation of any one of these regions, particularly during heat- and cold-evoked pain. These findings revealed the widespread cortical regions that are recruited by a noxious stimulus and provide clues to the neural circuitry of pain that undoubtedly include sensory, motor and cognitive components.