How can man know God, and how does he actually know him? A study of some second-century answers to a question that is fundamental to all theological reflection. Middle Platonism and Valentinian Gnosticism are investigated in their ontological architectures and in their gnoseological proposals as terms of comparison to highlight the theological epistemology of Irenaeus of Lyons. This essay sheds new light on the fertile theological-fundamental system of the newly proclaimed ‘Doctor of the Church’.