Non-Cartesian substance dualism (NCSD) maintains that persons or selves are distinct from their organic physical bodies and any parts of those bodies. It regards persons as ‘substances’ in their own right, but does not maintain that persons are necessarily separable from their bodies, in the sense of being capable of disembodied existence. In this paper, it is urged that NCSD is better equipped than either Cartesian dualism or standard forms of physicalism to explain the possibility of mental causation. A model of mental causation adopting the NCSD perspective is proposed which, it is argued, is consistent with all that is currently known about the operations of the human central nervous system, including the brain. Physicalism, by contrast, seems ill-equipped to explain the distinctively intentional or teleological character of mental causation, because it effectively reduces all such causation to ‘blind’ physical causation at a neurological level.