Rational choice theorists have not clearly articulated their epistemological positions, and for this reason, their arguments in favor of rational choice theory are inconsistent, contradictory, and unpersuasive. To remedy this problem, I describe how two of the main positions in the philosophy of science, instrumentalist-empiricism and scientific-realism, act as competing epistemological foundations for rational choice theory. I illustrate how these philosophical perspectives help political scientists (1) understand what is at stake in the theoretical debates surrounding the rationality assumption, self-interest, and methodological individualism, (2) identify inconsistencies in the epistemological positions adopted by rational choice theorists, and (3) assess the feasibility and desirability of a universal theory based on the rationality assumption.