Finished with his discussion of physics, Descartes now concludes his master work with a treatment of sensation. Though most of the properties that our sensations present to us do not exist in bodies, they are still an important aspect of our experience of the world, and so Descartes feels that he cannot reasonably call his treatise complete until he has accounted for these as well.

Sensations do not belong to bodies, but they do not belong to minds either. Rather, they belong to the combination of the two, the union of mind and body. Though Descartes believes that mind and body are distinct, he also believes that minds have an extremely intimate connection to certain bodies—that is, to human bodies. Human beings are an odd union of mind and body, forged together by God. The entire purpose of the senses is to help the union of mind and body (e.g. the entire human being) get around in the world. Though the senses are lousy at getting us scientific knowledge, they are terrific at their real job: to inform man of what is beneficial and harmful to him in the world. Just think about the subjectivity of sensations, Descartes tells us—hunger, thirst, pain, pleasure, colors—all of it is perfectly arranged to tell us what is good for us and what is bad for us. Here too, God has given us a perfect faculty. It only seems faulty because we use it incorrectly, miscasting it in the role of reason's helper.

Sensation belongs to the union between mind and body, rather than to either one exclusively, because both mind and body are necessary for sensation to occur. To see, for instance, you need both the physical organ, i.e. the eyes, as well as the mind, in order to perceive what the eyes report. (The perception is conscious and, thus, it is thought. Therefore, it can only belong to mind.) All bodily organs are connected to the brain, the physical seat of the mind, through a series of nerve connections. To return to the example of sight, when the eyes are affected by globules of the second element (i.e. light) retinal nerves fire, which in turn stimulates a whole series of nerves leading up to the brain. The brain, then, somehow, causes sensation to occur in the mind.

The operation is the same whether we are talking about emotional states (such as love, hate, fear), appetites (such as hunger, thirst), or external senses (sight, touch, smell, taste, sound). In the case of emotional states, the original organ in the chain is the heart; in the case of appetites the original organ is the stomach; and in the case of the external senses the original organs are the eyes, skin, frontal brain appendages, mouth, and ears respectively.

Descartes attempts to prove that the brain is the physical seat of the mind in principle IV.196. First, he points out, there are certain diseases that occur only in the brain, leaving the other organs unharmed but that nonetheless result in loss of sensation. Even sleep would be an example of this phenomena. Second, when neither the brain nor the original organ is damaged, but the nerve connection is obstructed, sensation is affected. Finally, there is such a thing as phantom pain, in which we feel a sensation even though we have lost the original organ. The seat of the mind, then, must truly be the brain, rather than the entire body.

Descartes ends the Principles with some final remarks on his project. He first takes care to distance his theory of matter from the much-maligned view of Democritus. Democritus's philosophy has received so much criticism, Descartes claims, not because it posits microscopic corpuscles that explain all observable phenomena (as Descartes' does too), but rather because it hypothesizes that these corpuscles are indivisible and that they move around in a void (two claims that Descartes has taken the time to disprove in Part II of the Principles). He then spends a few paragraphs talking about the level of certainty his claims warrant (absolute certainty, he is bold enough to assert) and then ultimately and fearfully reigning in this haughty claim by begging inferiority to the knowledge of the Church.