Mind-body dualism, or substance dualism in the philosophy of mind maintains that the mind and body, or the mental and physical, are distinct: the mind is not the body and the body is not the mind. 

On substance dualism, the mind (or the soul) is comprised of a non-physical substance, while the body is constituted of the physical substance known as matter. The mind and body are capable of causally affecting each other, which is a form of substance dualism is known as interactionism. 

Interactionism was given its classical formulation by the French philosopher René Descartes (1596-1650). Descartes, a substance dualist, found the interaction between the mental and physical to be a mystery although he speculated that the interaction occurs in the pineal gland deep within the brain.

Interactionism on substance dualism maintains that the mind and body, or mental events and physical events, causally influence each other. Some philosophers argue that this raises challenges. For example, if, on substance dualism, the mental substance is so radically distinct to the physical substance, then it would seem they lack the commonality necessary for interaction. Indeed almost everyone would agree that the mental and physical are different: the mental is, unlike the physical, immaterial, unextended and therefore has no size, shape, location, mass, motion, or solidity. Further, if a mind can indeed move a body, then why can it move only one particular body and not others?

Many important questions are raised, such as how mind-body interaction is possible? Where does the interaction occur? What is the nature of the interface between mind and matter? How are volitions translated into states of affairs? And so on. None of these questions are refutations of substance dualism but rather serve to invite further thinking on the topic. In other words, even if the substance dualist does not have an answer for how the mind and body interact, this does not serve to refute his position. The same logic applies to other disciplines and experts (e.g. psychologists, physicists, and sociologists) who do not have the answers to all the questions their studies raise.

A critic of substance dualism might argue that it is mysterious how the mind interacts with the body on substance dualism. The proponent of substance dualism, however, can respond similarly saying that it is equally mysterious how on materialism or naturalistic grounds matter, regardless of its organization, can produce conscious thoughts, feelings, and perceptions. The relationship between consciousness and brain processes leaves the materialist with a causal mystery perhaps as puzzling as that confronting the dualist.

Critics have objected to substance dualism that if one does not know how A causes B, then it is not reasonable to believe that A causes B, especially if A and B are different. In response, however, is that we often know that one thing causes another without having any idea of how causation takes place. Gravity can act on a planet millions of miles away and protons exert a repulsive force on each other even though we have no idea how such interactions take place. Yet it appears, despite us not knowing exactly how the mind and body interact, that we are constantly aware of causation between them.

A stronger way of putting the objection is that as substances, mind and body are so radically different in quality that it is difficult to imagine how two such alien things could influence one another.