How does Quine fare in the first decades of the twenty-first century? In this paper I examine a cluster of Quinean theses that, I believe, are especially fruitful in meeting some of the current challenges of epistemology and ontology. These theses offer an alternative to the traditional bifurcations of truth and knowledge into factual and conceptual-pragmatic-conventional, the traditional conception of a foundation for knowledge, and traditional realism. To make the most of Quine’s ideas, however, we have to take an active stance: accept some of his ideas and reject others, sort different versions of the relevant ideas, sharpen or revise some of the ideas, connect them with new, non-Quinean ideas, and so on. As a result the paper pits Quine against Quine, in an attempt to identify those Quinean ideas that have a lasting value and sketch potential developments.