The diagnosis of PD requires a thorough investigation of the main neurologic signs of the disease, as well as the search for signs that are atypical of PD, which may suggest diferential diagnoses (Quinn, 1995). Several diagnostic criteria for PD have been proposed (see Table 2.3), but even in the most experienced Movement Disorders Clinics, about 10–35% of patients initially diagnosed with PD will eventually be diagnosed with another disease (Rajput et al., 1991; Hughes et al., 1992a, 1992b) (Table 3.1). Atypical parkinsonian disorders are characterized by parkinsonian signs (e.g., resting tremor, rigidity, and bradykinesia) and additional clinical manifestations that are atypical of PD, such as pyramidal, cerebellar, or autonomic signs (Table 3.2). The two most prevalent atypical parkinsonian disorders are progressive supranuclear palsy (Steele et al., 1964) and multiple system atrophy, and parkinsonism may be found in dementia with Lewy bodies (McKeith et al., 1996), secondary parkinsonism (Winikates & Jankovic, 1999), and less frequently, corticobasal degeneration (Rebeiz et al., 1968), Alzheimer's disease (Merello et al., 1994), Pick's disease (Brion et al., 1991), Parkinson-dementia-complex of Guam, pallidonigral degeneration, Wilson's disease, and Huntington's disease. This chapter will focus on the most relevant differential diagnoses of PD. We will examine those disorders with neurologic, neuropsychiatric, and neuropsychologic symptoms similar to PD, as well as the relevance of vascular lesions and exposure to neuroleptic drugs for the production of parkinsonian signs.