Modern neuropathologic methods and molecular biology have lead to increased understanding of neurodegenerative disorders and biologically based classifications of these disorders. The purpose of this review is to discuss neuropathologic methods that are useful in the characterization of neurodegenerative disorders, with emphasis on disorders of late life that present with dementia or movement disorders. A diagnostic algorithm is suggested for neuropathologic evaluation of neurodegenerative disorders. The importance of clinical information is emphasized in arriving at the most precise and meaningful neuropathologic diagnosis.