Alertness is a non-selective attention component that refers to a state of general readiness which improves stimulus processing and response initiation. We used functional magnetic resonance imaging (fMRI) to identify neural correlates of visual and auditory alertness. A further aim was to investigate the modulatory effects of the cholinergic agonist nicotine. Non-smoking participants were given either placebo or nicotine (NICORETTE® gum 2 mg) and performed a target detection task with warned and unwarned trials in the visual and auditory modality. Our results provide evidence for modality specific correlates of visual and auditory alertness in respective higher-level sensory cortices and in posterior parietal and frontal brain areas. The only region commonly involved in visual and auditory alertness was the right superior temporal gyrus. A connectivity analysis showed that this supramodal region exhibited modality-dependent coupling with respective higher sensory cortices. Nicotine was found to mainly decrease visual and auditory alertness-related activity in several brain regions, which was evident as a significant interaction of nicotine-induced decreases in BOLD signal in warned trials and increases in unwarned trials. The cholinergic drug also affected alerting-dependent activity in the supramodal right superior temporal gyrus, here the effect was due to a significant increase of neural activity in unwarned trials. We conclude that the role of the right superior temporal gyrus is to induce an "alert" state in response to warning cues and thereby optimise stimulus processing and responding. We speculate that nicotine increases brain mechanisms of alertness specifically in conditions where no extrinsic warning is provided.