The second question that the Milesians posed, and that all later Presocratics tried to answer, is the plurality problem. The plurality problem asks how a single physis could give rise to the plurality of objects we observe in the world. Obviously, the question is based on the assumption made in the physis problem: that we can get the present cosmological structure in its full qualitative variety from a single fundamental substance (or, for Heraclitus, pattern or law).

Thales, as far as we know (again there is the problem of scarce fragments) did not treat the plurality problem, but starting from Anaxagoras the plurality problem became as central a concern to Presocratics as the question of physis. Anaxagoras was not only the first to treat this problem, but he also lay the framework through which many later philosophers would view it. According to Anaxagoras, the key to solving the plurality problem lay in the assumption of a basic polarity of opposites within the original physis (for him, the indefinite apeiron). These opposites (in particular, hot and cold) somehow separate off from the physis, through the eternal motion that the physis undergoes. The hot takes the form of fire, which in turn can coalesce into the sun and other heavenly bodies. The cold becomes dark mist (watery substance), which can then transform into air and earth once it is dried by the heat of fire.

Anaximines also solves the plurality problem by appealing to an eternal motion within his physis, but he makes a definite advance over his teacher by positing a detailed mechanism though which the elements become differentiated. His physis (aer) is transformed into everything else in the world through the processes of condensation and rarefaction. When aer rarifies it becomes fire, when it condenses it becomes wind, then water, then clouds, then earth, and then, finally, stone.

It is unclear how Xenophanes treated this problem (if he did at all), because we have very few fragments pertaining to his natural philosophy.

Heraclitus, like Anaxagoras, appeals to the idea of opposites inherent within nature in order to solve the plurality problem. According to Heraclitus's solution, though, there is really no such problem to begin with: the world begins as a plurality, a constant tension between opposites, which are also somehow unified through the logos.

For Parmenides there is no plurality problem since there is no plurality. What exists is entirely unified. The pluralists, however, return to the problem of plurality. According to all of the pluralists, the plurality that we observe around us is explained as the result of mixtures between their physis: for Empedocles, everything is made out of certain proportions of the four elements, for Anaxagoras, everything is made out of certain ratios of homeomeric substances, and for the Atomists, all objects arise as the result of mixtures of atoms.