The most selective disorder of central conceptual knowledge arises in semantic dementia, a degenerative condition associated with bilateral atrophy of the inferior and polar regions of the temporal lobes. Likewise, semantic impairment in both herpes simplex virus encephalitis and Alzheimer's disease is typically associated with bilateral, anterior temporal pathology. These findings suggest that conceptual representations are supported via an interconnected, bilateral, anterior temporal network and that it may take damage to both sides to produce an unequivocal deficit of central semantic memory. We tested and supported this hypothesis by investigating a case series of 20 patients with unilateral temporal damage (following vascular accident or resection for tumour or epilepsy), utilizing a test battery that is sensitive to semantic impairment in semantic dementia. Only 1/20 of the cases, with a unilateral left lesion, exhibited even a mild impairment on the receptive semantic measures. On the expressive semantic tests of naming and fluency, average performance was worse in the left- than right-unilateral cases, but even in this domain, only one left-lesion case had scores consistently more than two standard deviations below control means. These results fit with recent parallel explorations of semantic function using repetitive transcranial magnetic stimulation as well as functional imaging in stroke aphasic and neurologically intact participants. The evidence suggests that both left and right anterior temporal lobe regions contribute to the representation of semantic memory and together may form a relatively damage-resistant, robust system for this critical aspect of higher cognition. © 2010 The Author.