 Causal reasoning approaches try to reconstruct and sometimes justify the rules that allow scientists to infer causal relationships from data, including experimental data. One of the oldest such attempts is due to John Stuart Mill (1996 [1843]), who presented a systematic account of causal inference that consisted of five different so-called “methods”: The Method of Agreement, the Method of Difference, the Joint Method of Agreement and of Difference, the Method of Residues, and the Method Concomitant Variation. While some of these “methods” pertain more to observation, the Method of Difference in particular is widely seen as encapsulating an important principle of scientific reasoning based on experiment. Mill himself characterized it thus: “If an instance in which the phenomenon under investigation occurs, and an instance in which it does not occur, have every circumstance in common save one, that one occurring only in the former; the circumstance in which alone the two instances differ, is the effect, or the cause, or an indispensable part of the cause, of the phenomenon” (Mill 1996 [1843], Ch. 8, §2). Thus, Mill’s method of difference asks us to look at two situations: one in which the phenomenon under investigation occurs, and one in which it does not occur. If a factor can be identified that is the only other difference between the two situations, then this factor must be causally relevant.