In many situations, people can only compute one stimulus-to-response mapping at a time, suggesting that response selection constitutes a “central processing bottleneck” in human information processing. Using fMRI, we tested whether common or distinct brain regions were involved in response selection across visual and auditory inputs, and across spatial and nonspatial mapping rules. We isolated brain regions involved in response selection by comparing two conditions that were identical in perceptual input and motor output, but differed in the complexity of the mapping rule. In the visual—manual task of Experiment 1, four vertical lines were positioned from left to right, and subjects pressed one of four keys to report which line was unique in length. In the auditory—manual task of Experiment 2, four tones were presented in succession, and subjects pressed one of four keys to report which tone was unique in duration. For both visual and auditory tasks, the mapping between target position and key position was either spatially compatible or incompatible. In the verbal task of Experiment 3, subjects used nonspatial mappings that were either compatible (“same” if colors matched; “different” if they mismatched) or incompatible (the opposite). Extensive activation overlap was observed across all three experiments for incompatible versus compatible mapping in bilateral parietal and frontal regions. Our results indicate that common neural substrates are involved in response selection across input modalities and across spatial and nonspatial domains of stimulus-to-response mapping, consistent with behavioral evidence that response selection is a central process.