The therapeutic success of haloperidol in the treatment of Tourette syndrome (TS) put an end to the discussion about a "hysteric" or "neurotic" origin of TS. The cortico-striato-thalamo-cortical circuit has been identified as an underlying neurobiological correlate of TS. In this review we explore the main findings of structural alterations in TS including cortical areas, basal ganglia, hippocampus, amygdala, midbrain, and cerebellum. Based on the structural changes we examine the functional pattern described by the findings of fMRI and (15)O-PET/(18)FDG PET investigations. From the neuroimaging findings a cortical origin of the generation of tics is indicated. Future research on the neuronal footprint of TS should be directed towards addressing the question of which patterns of connectivity distinguish individuals in whom tics disappear during early adulthood from those in whom the tics persist. The understanding of this pathomechanism could provide a key on how to influence dysconnectivity in TS, for example, by more specific pharmaceutical intervention or by individually adopted EEG and/or fMRI neurofeedback.