The main philosophical referents of Ginés de Sepúlveda were Aristotle, Saint Thomas Aquinas, Roman law and Christian theology.

Then, in February 1515, he obtained a letter of recommendation from Cardinal Cisneros to attend the prestigious Spanish College in Bologna, Italy, known for its studies in canon law and theology.

While in Bologna, he enjoyed the friendship and patronage of Alberto Pío, Prince of Carpi, and also met Giulio de' Medici who would later become Pope Clement VII.

After Medici became Pope Clement VII in 1523, Sepúlveda served at the papal curia in Rome where he developed a reputation for scholarship and rhetorical skills.

[2] He also used his rhetorical skills 1529 to write Ad Carolum V, urging the Habsburg emperor Charles V to unite Europe and fight the Turks.

[5] Sepúlveda was the defender of the Spanish Empire's right of conquest, of colonization, of forced conversion in the New World, and a supporter of colonial slavery.

Sepúlveda also drew on the theology and philosophy of Saint Thomas Aquinas, who argued that there were different degrees of perfection and that some human beings were naturally superior to others.

Sepúlveda used too concepts from Roman law, especially the idea of just war theory and the right of conquest, to argue that the colonization of the Americas by the Spanish Empire was legally and morally justified.

Sepúlveda defended the position of the colonists, although he had never been to America, claiming that some Amerindians were "natural slaves" as defined by Aristotle in Book I of Politics.