Maintaining attention for more than a few seconds is essential for mastering everyday life. Yet, our ability to stay focused on a particular task is limited, resulting in well-known performance decrements with increasing time on task. Intriguingly, such decrements are even more likely if the task is cognitively simple and repetitive. The attentional function that enables our prolonged engagement in intellectually unchallenging, uninteresting activities has been termed vigilant attention. Here we synthesized what we have learned from functional neuroimaging about the mechanisms of this essential mental faculty. To this end, a quantitative meta-analysis of pertinent neuroimaging studies was performed, including supplementary analyses of moderating factors. Furthermore, we reviewed the available evidence on neural time-on-task effects, additionally considering information obtained from patients with focal brain damage. Integrating the results of both meta-analysis and review, we identified a set of mainly right-lateralized brain regions that may form the core network subserving vigilant attention in humans, including dorsomedial, mid- and ventrolateral prefrontal cortex, anterior insula, parietal areas (intraparietal sulcus, temporoparietal junction), and subcortical structures (cerebellar vermis, thalamus, putamen, midbrain). We discuss the potential functional roles of different nodes of this network as well as implications of our findings for a theoretical account of vigilant attention. It is conjectured that sustaining attention is a multicomponent, nonunitary mental faculty, involving a mixture of (a) sustained/recurrent processes subserving task-set/arousal maintenance and (b) transient processes subserving the target-driven reorienting of attention. Finally, limitations of previous studies are considered and suggestions for future research are provided.