Dopamine replacement therapy in Parkinson's disease ameliorates motor symptoms. However, it has recently been recognized that a small subgroup of patients suffer motor and behavioral disturbances attributable to taking quantities of medication well beyond the dose required to treat their motor disabilities. Dopamine dysregulation syndrome can be regarded as a pattern of compulsive medication use leading to disabling motor and behavioral features. The major theories of psychostimulant addiction may help explain some of the phenomena seen in the dopamine dysregulation syndrome. In contrast to the predictable pattern of severe degeneration of ventrolateral nigral dopaminergic cells, there is a smaller and more variable loss of dopamine neurons within the ventral tegmental areas. Sensitization of ventral striatal networks to antiparkinsonian therapy and appetitive behaviors may be analogous to the neuroplastic changes in the dorsal striatum thought to contribute to the motor complications of treatment such as dyskinesias. This syndrome greatly affects patients, their families and society. Treatment is difficult; deep brain stimulation of the subthalamic nucleus may therefore prove useful in some cases.