Corticofugal projections to neurons in the medullary dorsal horn, i.e., the trigeminal spinal subnucleus caudalis (Sp5C), are thought to play a critical role in regulating nociceptive information processing in the trigeminal nervous system. The Sp5C consists of 5 layers, each of which exhibits its own characteristic features of cellular organization. Therefore, the layers receiving corticofugal projections must be identified when discussing the role of the cerebral cortex in nociception arising from the trigeminal nerve. It is also necessary to discriminate between layers of the Sp5C where corticofugal projections terminate, because the Sp5C involves glutamatergic neurons and GABAergic/glycinergic neurons, which correspond to excitatory and inhibitory neurons, respectively. This review summarizes descending projections from the cerebral cortex, including the primary and secondary somatosensory and insular cortices, to the Sp5C.