Although Parkinson's disease (PD) is thought to represent a specific clinical-pathologic entity, up to 20% of patients diagnosed as having PD will have another disorder at autopsy. Furthermore, pathologic features typically associated with PD can also be observed in patients with other neurodegenerative disorders. This article attempts to point out the difficulties in differentiating PD from progressive supranuclear palsy and other parkinsonism plus syndromes and various causes of parkinsonism associated with cognitive changes. The clinical and pathologic differentiation of these disorders are discussed. These disorders are usually associated with postsynaptic receptor changes and therefore levodopa and dopamine agonists provide limited benefit.