Neuroimaging studies reliably reveal ventrolateral prefrontal cortex (VLPFC) activation for processing of abstract relative to concrete words, but the cause of this effect is unclear. Here, in a convergent neuropsychological and repetitive transcranial magnetic stimulation (rTMS) investigation, we tested the hypothesis that abstract words require VLPFC because they depend heavily on the semantic–executive control processes mediated by this region. Specifically, we hypothesized that accessing the meanings of abstract words require more executive regulation because they have variable, context-dependent meanings. In the neuropsychology component of the study, aphasic patients with multimodal semantic deficits following VLPFC lesions had impaired comprehension of abstract words, but this deficit was ameliorated by providing a sentence cue that placed the word in a specific context. Concrete words were better comprehended and showed more limited benefit from the cues. In the second part of the study, rTMS applied to left VLPFC in healthy subjects slowed reaction times to abstract but not concrete words, but only when words were presented out of context. TMS had no effect when words were preceded by a contextual cue. These converging results indicate that VLPFC plays an executive regulation role in the processing of abstract words. This role is less critical when words are presented with a context that guides the system toward a particular meaning or interpretation. Regulation is less important for concrete words because their meanings are constrained by their physical referents and do not tend to vary with context.