In his refutation of skepticism in book IV of De rerum natura (469–521), Lucretius uses argumentative methods typical of Epicurus: the περιτροπή is in many ways similar to that used by the philosopher in book XXV of Περὶ φύσεως, the same book where, in a passage dedicated to the criticism against determinists, can be found a reference to the criterion of the πρόληψις, that Lucretius exploits in his refutation. Moreover, Lucretius develops a strong demonstration concerning the irrefutability of αἴσθησις as a criterion of truth, which finds significant points of contact with a large fragment, transmitted by Diogenes Laertius (X 31–32) and generally traced back to the Canon of Epicurus. The last argument used by the poet is a pragmatic one: for the skeptic it would be impossible to live. The argument is similar to the praxis-based argument used by Epicurus in the Περὶ φύσεως against the partisans of determinism. But the pragmatic argument goes back to a very ancient layer of anti-skeptical polemics, even prior to Epicurus and already present in book Γ of Aristotle’s Metaphysics . Although later influences cannot be excluded, Lucretius appears to be a faithful witness of Epicurus. Probably in a lost section of the Περὶ φύσεως, the philosopher of Samos showed positions going against skeptical or proto-skeptical attitude, contemporary or earlier to the time of the philosopher, probably developed in a Democritean or a Socratic context. Epicurus’ ad hominem strategy is very close to that of the philosopher in the Principal Doctrines XXIII–XXV, and certainly follows Aristotle’ strategy in book Γ of Metaphysics against those who deny the principle of non-contradiction. In a similar way, Epicurus does not have one figure as the objective of his refutation but constructs a hypothetical dialectical opponent capable of embodying a series of philosophical tendencies judged by the founder of Kepos to be extremely dangerous not only for the correct exercise of thought but for the human being’s life itself.