The doctrine of creation out of nothing was conceptually sharpened as the Church Fathers engaged the cosmological views of their opponents. This article discusses the emergence of this doctrine in the second century, focusing on the polemic of Irenaeus against the Gnostics. For Irenaeus, creatio ex nihilo was already a part of the “rule of truth,” which provided a hermeneutical key to the scriptures. Irenaeus also used rational arguments to show that Gnostic cosmologies obscured, rather than explained the origins of the world. A different challenge arose in the fourth century, when Arius began to teach that the Son was created out of nothing, thereby treating the divine act of the generation of the Son analogously to the creating of the world. Athanasius of Alexandria introduced an important distinction by correlating the eternal generation of the Son with the divine essence and the creation of the world with the will of the Father.