Substance dualism asserts that mind and matter are fundamentally distinct kinds of foundations. There are several types of substance dualism. Most substance dualists hold the view that the mind and body are capable of causally affecting each other, known as interactionism.

Cartesian dualism most famously defended by René Descartes, argues that there are two kinds of substances: mental and physical. Descartes states that the mental can exist outside of the body, and the body cannot think. Substance dualism is important historically for having given rise to much thought regarding the famous mind–body problem. It is compatible with theologies which claim that immortal souls occupy an independent realm of existence distinct from that of the physical world. Cartesians tend to equate the soul to the mind.