This article discusses Descartes's preferred focus on morally and theologically neutral subjects and points out the impact of this focus on the scientific status of theology. It does so by linking Descartes's method to his transformation of the notion of substance. Descartes's Meditations centred around epistemological questions rather than non-human intelligences or the life of the mind beyond this world. Likewise, in his early works, Descartes consistently avoided referring to causal operators. Finally, having first redefined the notion of substance in the Principia, Descartes would completely abandon making use of this notion in his later years. Indeed, in contrast to many authors before and after him, Descartes never showed any interest in the long-established metaphysical interpretation of substances as being causal factors of natural change. With God, nature, and mind commonly serving as instances of substantial causality, Descartes's philosophy had a huge impact on the place of God in science and discreetly excluded theology as a subject to which his method might be applied.