An appreciation of the comparative functions of the corticospinal tract is of direct relevance to the understanding of how results from animal models can advance knowledge of the human motor system and its disorders. Two critical functions of the corticospinal tract are discussed: first, the role of descending projections to the dorsal horn in the control of sensory afferent input, and second, the capacity of direct cortico-motoneuronal projections to support voluntary execution of skilled hand and finger movements. We stress that there are some important differences in corticospinal projections from different cortical regions within a particular species and that these projections support different functions. Therefore, any differences in the organization of corticospinal projections across species may well reflect differences in their functional roles. Such differences most likely reflect features of the sensorimotor behavior that are characteristic of that species. Insights into corticospinal function in different animal models are of direct relevance to understanding the human motor system, providing they are interpreted in relation to the functions they underpin in a given model. Studies in non-human primates will continue to be needed for understanding special features of the human motor system, including feed-forward control of skilled hand movements. These movements are often particularly vulnerable to neurological disease, including stroke, cerebral palsy, movement disorders, spinal injury, and motor neuron disease.