Substance dualism is a type of ontological dualism defended by Descartes in which it is claimed that there are two fundamental kinds of substance: mental and material. The mental does not extend in space, and material cannot think. Descartes imagined that the soul, a mental substance, could interact with the body through the pineal gland. This view contradicts physicalism which is the received view in philosophy of mind. However, it may be regarded important historically in that it has given rise to much thought over the famous mind/body problem .

Substance dualism is a philosophical position compatible with most theology which posits immortal souls occupying an independent realm of existence, while apparently bodies die. In Descartes's theory, the seat of consciousness is immaterial and immortal: it does not exist physically, while the body is merely a machine. Descartes considered animals to be machines with no souls, separating man from animal.

David Chalmers recently showed a metaphysical scenario inspired from the movie The Matrix in which substance dualism is true. Consider a computer simulation in which the bodies of the creatures are controlled by their minds which remain strictly external to the simulation. The creatures can do all the science they want in the world, but they will never be able to figure out where their minds are, for it does not exist in their observable universe. This is a case of substance dualism with respect to the computer simulation. This naturally differs from a computer simulation in which the minds are part of the simulation, in that case substance monism would be true.