Physicalism and antireductionism are the ruling orthodoxy in the philosophy of biology. But these two theses are difficult to reconcile. Merely embracing an epistemic antireductionism will not suffice, as both reductionists and antireductionists accept that given our cognitive interests and limitations, non-molecular explanations may not be improved, corrected or grounded in molecular ones. Moreover, antireductionists themselves view their claim as a metaphysical or ontological one about the existence of facts molecular biology cannot identify, express or explain. However, this is tantamount to a rejection of physicalism and so causes the antireductionist discomfort. In this paper we argue that vindicating physicalism requires a physicalistic account of the principle of natural selection, and we provide such an account. The most important payoff to the account is that it provides for the very sort of autonomy from the physical that antireductionists need without threatening their commitment to physicalism.