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Decision-making in the context of leadership, has received scant attention in the management literature, which has traditionally centered on general mental ability and personality as predictors of effectiveness. This research effort bridges the neuroscientific and management literatures to offer an alternative, neuropsychological profile of effective leadership by proposing prefrontal brain processes (executive function) as a key component and predictor of complex decision-making and leadership effectiveness. While the management literature has largely viewed decision-making as a cognitive ability, neuroscience informs us that this complex function emerges from the integration of affective and cognitive signals in the prefrontal cortex. In an attempt to identify the neural predictors of effective leadership decision-making, 105 corporate leaders were assessed on a robust array of neuropsychological indices of prefrontal brain function. These were in turn correlated with their leadership and decision-making abilities after controlling for general mental ability and personality, utilizing structural equation modeling. Executive function incrementally predicts complex decision-making and transformational leadership effectiveness, above and beyond general mental ability. Complex decision-making does not appear to be central to leadership effectiveness, while extraversion emerges as the strongest predictor of transformational leadership followed by executive function. Executive function, extraversion and general mental ability do not predict transactional leadership. These results would need replication in a larger dataset to establish their validity, especially in the case of executive function. While the heritability of leadership ability has emerged as fairly significant, this opens the field to unearthing the biological variables and predictors of leadership ability. Neuroscience thus has the potential to offer biomarkers and metrics of leadership that can further not only our foundational knowledge of organizational behavior, but can also find useful applications in recruitment, training and development practice, though this cross-disciplinary initiative is in its infancy. Based on the preliminary results from this study, executive function (which has so far remained in the domain of neurology) has the potential to inform and measure leadership effectiveness.