Primary progressive aphasia (PPA) is a disorder of declining language that is a frequent presentation of neurodegenerative diseases such as frontotemporal lobar degeneration. Three variants of PPA are recognized: progressive nonfluent aphasia, semantic dementia, and logopenic progressive aphasia. In an era of etiology-specific treatments for neurodegenerative conditions, determining the histopathological basis of PPA is crucial. Clinicopathological correlations in PPA emphasize the contributory role of dementia with Pick bodies and other tauopathies, TDP-43 proteinopathies, and Alzheimer disease. These data suggest an association between a specific PPA variant and an underlying pathology, although many cases of PPA are associated with an unexpected pathology. Neuroimaging and biofluid biomarkers are now emerging as important adjuncts to clinical diagnosis. There is great hope that the addition of biomarker assessments to careful clinical examination will enable accurate diagnosis of the pathology associated with PPA during a patient's life, and that such findings will serve as the basis for clinical trials in this spectrum of disease.