Tourette syndrome (TS) is characterized by chronic motor and vocal tics that fluctuate over time. The disorder is frequently accompanied by comorbid disorders (86–90%), which can include obsessive-compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), anxiety, disruptive behaviors, and mood disorders. While investigations into the underlying pathophysiology of this disorder continue, most hypotheses suggest dysfunction in cortico–basal ganglia–thalamo-cortical circuits. Neuroimaging studies have been variable, but alterations have been detected in cortex, basal ganglia, and related structures. Noninvasive electrophysiological studies suggest an altered cortical adaptive mechanism, whereas electrophysiological studies in patients treated with deep-brain stimulation raise the question of altered thalamic activity. Several neurotransmitters within cortical–striatal circuits have been implicated as contributing etiological factors, including dopamine, GABA (gamma-aminobutyric acid), glutamate, acetylcholine, and others. Nevertheless, despite ongoing investigations, much still remains to be learned about the underlying pathophysiological abnormalities in TS.