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Leaders must take responsibility for others and thus affect the well-being of individuals, organizations, and nations. We identify the effects of responsibility on leaders’ choices at the behavioral and neurobiological levels and document the widespread existence of responsibility aversion, that is, a reduced willingness to make decisions if the welfare of others is at stake. In mechanistic terms, basic preferences toward risk, loss, and ambiguity do not explain responsibility aversion, which, instead, is driven by a second-order cognitive process reflecting an increased demand for certainty about the best choice when others’ welfare is affected. Finally, models estimating levels of information flow between brain regions that process separate choice components provide the first step in understanding the neurobiological basis of individual variability in responsibility aversion and leadership scores.