According to many theories, semantic representations reflect the parallel activation of information coded across a distributed set of modality-specific association brain cortices. This view is challenged by the neurodegenerative condition known as semantic dementia (SD), in which relatively circumscribed, bilateral atrophy of the anterior temporal lobes results in selective degradation of core semantic knowledge, affecting all types of concept, irrespective of the modality of testing. Research on SD suggests a major revision in our understanding of the neural basis of semantic memory. Specifically, it is proposed that the anterior temporal lobes form amodal semantic representations through the distillation of the multimodal information that is projected to this region from the modality-specific association cortices. Although cross-indexing of modality-specific information could be achieved by a web of direct connections between pairs of these regions, amodal semantic representations enable semantic generalization and inference on the basis of conceptual structure rather than modality-specific features. As expected from this hypothesis, SD is characterized by impaired semantic generalization, both clinically and in formal assessment. The article describes a comprehensive array of under- and overgeneralization errors by patients with SD when engaged in receptive and expressive verbal and nonverbal tasks and everyday behaviors. © 2008 New York Academy of Sciences.