Notoriously, Descartes's dualism is afflicted with a deeply serious and potentially fatal difficulty: the difficulty of explaining mind–body interaction. To many it has seemed that, just in so far as Descartes is able to support the claim that body and mind are metaphysically utterly different from each other, to that same extent he is unable to explain how two such different substances could affect one another. If mind or rational soul and physical body are really as different from each other as he claims, how can changes in physical sense organs (for example) cause changes in the subject's ideas? And how can the mind make the body do things? Yet Descartes is in full agreement with those who say that when I look at the sea it is the sea that causes my perception of blue, and when I decide to cross the road it is my decision and the thoughts leading to it that cause my body to perform that action.

On the surface it appears that the modern-day “problem of mental causation” outlined in the Introduction (and sometimes called “the physical exclusion problem”) is just a modern version of this Cartesian difficulty. Granted, this more recently fashionable problem is usually raised as a challenge to property dualists rather than substance dualists. But it, just like the problem raised by Descartes's critics, asks how our mental lives can possibly exercise any causal influence over physical events, particularly our own actions.