Objective.-To identify possible gray matter alterations in patients with chronic migraine using voxel-based morphometry (VBM). Background.-VBM studies demonstrate structural alterations of gray matter (GM) in episodic migraine (EM) patients. Some of these alterations correlate with disease duration and headache frequency. We assessed GM alterations in chronic migraine (CM) and EM to evaluate the concept of migraine as a progressive disorder of the brain. Methods.-Individually age and sex-matched subjects with CM or EM (both without aura) and healthy controls (n=21 per group) underwent magnetic resonance imaging-based VBM. Results.-We found an increase of GM volume (GMV) in amygdala and putamen, in CM compared to controls. GMV of EM compared to controls did not differ statistically significantly. Headache frequency in all migraineurs (EM and CM) correlated positively with GMV in putamen, frontal and temporal gyrus and negatively in left cuneus. Conclusion.-CM is associated with structural changes in brain regions involved in pain processing but also in affective and cognitive aspects of pain. Some GM alterations are correlated with headache frequency assessed in EM and CM. The findings support the assumption that chronic pain alters brain plasticity. GMV increase may reflect a remodeling of the central nervous system due to repetitive headache attacks leading to chronic sensitization and a continuous ictal-like state of the brain in chronic migraineurs.