The following post was added to the Epicurean Philosophy thread at facebook today by a D. O'Connell. Feel free to check it out if you like for other responses, but I am posting it here so I can add my response to it. I am sure some of you here can do better:
The problem with atomism is that we don't actually *know* whether the universe is comprised of irreducible atoms. I don't actually think we can reasonably accept philosophical naturalism as "true" since we just don't know. Is methodological naturalism/skepticism compatible with Epicureanism? Can we be accept that we don't know whether atomism is true or not, and still follow through to the four cures etc? Does it still hold together?
I would propose in response to your question that the word you put in quotes ("know") is where some people are going to agree with Epicurus and some will never agree with him.
Epicurus taught irreducible primary entities because such a theory gives the basis for how the universe may work using non-supernatural means. Irreducible entities that have existed eternally need no supernatural creator or custodian.
Epicurus also had a theory of epistemology grounded in premises stemming from a non-supernatural universe in which he held that while the universe is in constant flux, the flux is not so fast and unintelligible that our senses cannot navigate it. From such a perspective the question of "knowing" has a practical focus - can we learn enough through our senses to survive? - and not an absolute focus based assertions of a supernatural "absolute" truth.
If one takes the position that "we just don't know" things about the nature of the way the universe works, because we don't know (and can never know) all the facts that we might like to know, then one is on the slippery slope to radical skepticism. That road that leads to nihilism and ultimately to despair and death, and the only way for a practical person to get off that road is to grapple with what it means to "know" something, and then reach for support from a practical perspective on knowledge such as Epicurus suggests.
From Torquatus in Cicero's On Ends:
Moreover, unless the constitution of the world is thoroughly understood, we shall by no means be able to justify the verdicts of our senses. Further, our mental perceptions all arise from our sensations; and if these are all to be true, as the system of Epicurus proves to us, then only will cognition and perception become possible. Now those who invalidate sensations and say that perception is altogether impossible, cannot even clear the way for this very argument of theirs when they have thrust the senses aside. Moreover, when cognition and knowledge have been invalidated, every principle concerning the conduct of life and the performance of its business becomes invalidated. So from natural science we borrow courage to withstand the fear of death, and firmness to face superstitious dread, and tranquility of mind, through the removal of ignorance concerning the mysteries of the world, and self-control, arising from the elucidation of the nature of the passions and their different classes, and as I shewed just now, our leader again has established the canon and criterion of knowledge and thus has imparted to us a method for marking off falsehood from truth.
Further, I would suggest that referencing "four cures" is much less effective than focusing on the full statements of the first four principle doctrines, because those doctrines are positive assertions about the nature of the universe and much more than a cure for anxiety.
For me, the system of Epicurus holds together even more firmly than it ever did, because after almost three thousand years of scientific advancement we have no reason to question his ultimate conclusions as to how to live:
(1) There are no supernatural gods who either created the universe or reward their friends or punish their enemies.
(2) There is no existence after death in which we might be burned for eternity in hell, nor any heaven to look for as a reward for following unprovable religious promises.
(3) It is pleasure and pain (widely understood, to include all types of physical and mental feelings) which serve as the ultimate guides for life and by which all decisions must be evaluated.
(4) There are no absolute ethical rules in life (such as "virtue" in the abstract) to follow in place of the guidance of pleasure and pain (item 3)