Previous studies have shown that processing information in one sensory modality can either be enhanced or attenuated by concurrent stimulation of another modality. Here, we reconcile these apparently contradictory results by showing that the sign of cross-modal interactions depends on whether the content of two modalities is associated or not. When concurrently presented auditory and visual stimuli are paired by chance, cue-induced preparatory neural activity is strongly enhanced in the task-relevant sensory system and suppressed in the irrelevant system. Conversely, when information in the two modalities is reliably associated, activity is enhanced in both systems regardless of which modality is task relevant. Our findings illustrate an ecologically optimal flexibility of the neural mechanisms that govern multisensory processing: facilitation occurs when integration is expected, and suppression occurs when distraction is expected. Because thalamic structures were more active when the senses needed to operate separately, we propose them to serve gatekeeper functions in early cross-modal interactions.