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Pyrrhonian Skepticism was founded by Pyrrho of Elis (c. 360–275 BC), who argued that knowledge is impossible. The Skeptics proposed various arguments for their conclusions, including Platonic doubts about the world of our senses, and through offering opposing arguments for any position. Timon of Philius (c. 315–225 BC) further introduced the dilemma that, in the absence of self-evident principles, any argument will either be circular or face an infinite regress of justification. In consequence, the Skeptics proposed that we should suspend judgment on all matters of life and thereby attain a state of ataraxia, or peace of mind. This was regarded as both a practical response to a philosophical problem and a healthy corrective to the excesses of dogmatism.

After the Pyrrhonian Skeptics, the school flourished in Athens (as the so-called Academic Skeptics), where Arcesilaus (c. 268–241 BC) taught the Socratic Dialogues not as advocating a positive doctrine but as the methodical refutation of any unwarranted position. In both its Pyrrhonian and post-Pyrrhonian iterations, Skepticism offered an alternative approach to the political uncertainties of the time. Rather than withdrawing from the world (the Cynical course), the Skeptics proposed attaining an untroubled equanimity based on accepting our epistemic limitations.