The debate initiated by Segal's "defense of reductionism" has produced a polarization between the theoretical positions of reductionism and religionism, suggesting that no alternative exists. This is unfortunate, for empirical research is neither reductionist nor religionist. The article discusses this neglected empirical option. Empirical research must be based on methodological agnosticism with regard to religious and philosophical "first principles", and must fully recognize the historicity of religious phenomena. This empirical perspective is applied to the newly emerging academic field of esotericism. Antoine Faivre's definition of esotericism as a historically recognizable "form of thought" leads to a discussion of the empirical status of the history of (religious) ideas, especially in the tradition of Arthur O. Lovejoy. This is followed by a discussion of the implications of empirical method for the diachronic and the synchronic study of esotericism. It is argued that the latter pursuit entails a fundamental questioning of conventional distinctions, particularly between "gnosticism" and "mysticism".