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This chapter traces the lasting impact of Francisco de Vitoria’s examination of the conquest of the New World on the early modern Spanish imperial discourse. If Vitoria did not deploy the concept of a ‘state of nature,’ he probed whether claims about the ostensibly natural condition of lands and peoples overseas, or arguments about the organic connectedness of humankind might justify Castile’s imperial venture. The present chapter reconstructs how Spanish voices from the New World took a fresh approach to these issues in the later sixteenth and seventeenth centuries. In contrast to recent scholarship, it contends that thinkers like Alonso de la Vera Cruz, José de Acosta, and Juan de Solórzano y Pereira put forward novel visions of empire without jettisoning the Vitorian architecture of debate. These theorists not only revisited whether American lands, peoples, or oceanic space persisted in a pre-political state. But they also insisted on the centrality of a theologically grounded conception of justice and morality – even when defending Spain’s right to rule the Indies against the emerging claims of rival European empires.