Semantic knowledge (e.g., long-established knowledge about objects, facts, and word meanings) is known to be severely impaired by damage to the anterolateral temporal lobe. For example, patients with semantic dementia have prominent atrophy in anterolateral temporal cortex and also have significant damage within the medial aspect of the temporal lobe. However, there is uncertainty about the contribution of medial temporal lobe damage, including perirhinal cortex damage, to impaired semantic knowledge. Drawing largely on published material from multiple sources, we compared the performance of severely amnesic patients with large medial temporal lobe lesions and patients with semantic dementia on nine tests of semantic knowledge and two tests of new learning ability. On the tests of semantic knowledge, the amnesic patients performed markedly better than the patients with semantic dementia. By contrast, on the tests of new learning, the patients with semantic dementia performed markedly better than the amnesic patients. We conclude that medial temporal lobe damage impairs the formation of declarative memory, and that semantic knowledge is impaired to the extent that damage extends laterally in the temporal lobe. Reports that the extent of atrophy in perirhinal cortex correlated with the severity of impaired semantic knowledge may be understood by supposing that the extent of damage in many temporal lobe areas is intercorrelated in this progressive disease, and that the extent of atrophy in perirhinal cortex is a proxy for the overall severity of dementia.