Pyrrhonian skepticism has roots in metaphysical discussions relevant to relativism. The lecture reconstructs these discussions in Plato’s Theaetetus, and explores how different versions of Pyrrhonian skepticism—the skepticism of Pyrrho, of Aenesidemus, and of Sextus Empiricus—compare to Protagorean relativism. I begin with a sketch of why Plato interprets Protagoras’ Measure Doctrine as global relativism rather than relativism about a particular domain. Pyrrhonian skepticism, it is argued, inherits this global scope. But Pyrrhonian responses to disagreement differ importantly from the responses Protagorean relativism envisages. Skepticism suggests that, when encountering disagreement, it is rational to step back from one’s view and investigate, rather than simply hold on to one’s view, as presumably the relativist does. The paper defends skepticism’s response to disagreement as construed by Sextus Empiricus as superior to earlier proposals.