Despite converging agreement about the definition of PVS, recent reports have raised concerns about the possibility that, in a selection of cases, residual cognitive functions may remain undetected. Objective assessment of residual cognitive function can be extremely difficult in cases where motor responses are inconsistent or may even be undetectable. Here, hypothesis-driven strategies will be described for using H215O PET and fMRI activation studies to assess covert cognitive processing in patients with a clinical diagnosis of PVS. Several recent cases will be described, who have exhibited clear and predicted rCBF and/or BOLD responses during well documented activation paradigms (e.g. face recognition and speech perception) that have been shown to produce specific, robust and reproducible activation patterns in normal volunteers. In spite of the multiple logistic and procedural problems involved, these results provide a strong basis for the systematic study of residual cognitive function in patients diagnosed as being in a PVS.