Normal ageing is associated with a wide variety of disturbances in the structure and function of the human brain. Recent neuroimaging studies suggest that the prefrontal cortex (PFC) is particularly vulnerable to the effects of ageing. These findings are compatible with the so-called 'frontal ageing hypothesis' which has been formulated on the basis of neuropsychological research on non-pathological ageing. We will argue on the basis of recent structural and functional neuroimaging studies that this hypothesis needs to be refined, especially to acknowledge the possible relevance of a distinction between subregions within the PFC. In addition, findings with regard to a differential involvement of grey versus white matter suggest that both have to be considered in relation to age-related cognitive decline. Hence, neural networks and larger systems of interconnected brain regions and the functional activity in these circuits may be more important than specific cortical regions to explain age effects on cognitive functioning. Finally, it is important to consider individual variability due to sex differences and age-extrinsic biomedical factors in research which examines the relationship between brain structure or function and cognitive ageing.