Some physicalists (Balog 2012, Howell 2013), and most dualists, endorse the acquaintance response to the Knowledge Argument. This is the claim that Mary gains substantial new knowledge, upon leaving the room, because phenomenal knowledge requires direct acquaintance with phenomenal properties. The acquaintance response is an especially promising way to make sense of the Mary case. I argue that it casts doubt on two claims often made on behalf of physicalism, regarding parsimony and mental causation. I show that those who endorse the acquaintance response face special obstacles to invoking parsimony in an argument for physicalism. And I show how acknowledging the phenomenon of acquaintance can ease the dualist’s problems with mental causation, by dispelling three key objections to epiphenomenalism. The most challenging of these objections is that epiphenomenalism blocks an evolutionary explanation of the so-called “hedonic/utility match”. I propose that pleasures and pains, while themselves epiphenomenal, can nonetheless explain positive and negative associations with stimuli, associations that can contribute to fitness.