Nicotine enhances attentional functions. Since chronic nicotine exposure through smoking induces neuroadaptive changes in the brain at a structural and molecular level, the present functional MRI (fMRI) study aimed at investigating the neural mechanisms underlying visuospatial and sustained attention in smokers and non-smokers. Visuospatial attention was assessed with a location-cueing paradigm, while sustained attention was measured by changes in response speed over time. During invalid trials, neural activity within the basal forebrain was selectively enhanced in smokers and higher basal forebrain activity was associated with increased parietal cortex activation. Moreover, higher levels of expired carbon monoxide in smokers before scanning were associated with higher parietal cortex activation and faster responses to invalidly cued targets. Smokers showed a slowing of responses and additionally recruited an area within the right supramarginal gyrus with increasing time on task. Activity decreases over time were observed in visual areas in smokers. The data provide evidence for altered attentional functions in smokers as compared with non-smokers, which were partly modulated by residual nicotine levels and were observed at a behavioural level for sustained and at a neural level for spatial and sustained attention.