Behavioural and neuropsychological evidence suggests that abstract and concrete concepts might be represented, retrieved and processed differently in the human brain. Using fMRI, we demonstrate that retrieval of abstract relative to sensory-based semantics during synonym judgements increased activation in a left frontotemporal system that has been associated with semantic processing particularly at the sentence level. Since activation increases were observed irrespective of the degree of difficulty, we suggest that these differential activations might reflect a particular retrieval mechanism or strategy for abstract concepts. In contrast to sensory-based semantics, the meaning of abstract concepts is largely specified by their usage in language rather than by their relations to the physical world. Subjects might therefore generate an appropriate semantic sentential context to fully explore and specify the meaning of abstract concepts. Our results also explain why abstract semantics is vulnerable to left frontotemporal lesions.