In this episode of SERious Epidemiology, Hailey and Matt welcome guest host Dr. John Jackson to discuss Chapter 5 of Causal Inference: What If? This chapter focuses on explaining the concept of interaction. Together, they unpack the often-confusing distinction between causal interaction and effect measure modification. Throughout the discussion they go on (helpful) tangents to talk about factorial trials, risk stratification, DAGs, confounding control, and why students are right to find all of this a bit head-spinning. They also debate additive versus multiplicative interaction, sufficient component causes, causal pies, synergism, antagonism, and whether interaction terms can really tell us anything about mechanisms—or whether they mostly tell us where treatment effects may differ. Along the way, there are excellent examples involving surgery, vaccination, infectious disease. Also, in case you ever wondered, every academic has an ever-growing “papers to read” pile.