This paper is a keynote address prepared for a conference on “Entangled Political Economy” sponsored by the Wirth Institute. In keeping with the conventions of such an address, I look both backward and forward, while placing more emphasis on looking forward. In looking backward, I compare and contrast two orientations toward political economy: additive and entangled. In looking forward, I explore some of the analytical challenges that confront efforts to pursue a vision of entangled political economy. While these challenges are substantive in character, those efforts necessarily rest on methodological presumptions. Accordingly, the paper opens by reviewing some of those methodological presumptions before turning to the substantive articulations and challenges.