Motor commands are transmitted from the motor cortical areas to effectors mostly via the corticospinal (CS) projection. Several subcortical motor nuclei also play an important role in motor control, the subthalamic nucleus, the red nucleus, the reticular nucleus and the superior colliculus. These nuclei are influenced by motor cortical areas via respective corticofugal projections, which undergo complex adaptations after motor trauma (spinal cord/motor cortex injury) or motor disease (Parkinson), both in the absence or presence of putative treatments, as observed in adult macaque monkeys. A dominant effect was a nearly complete suppression of the corticorubral projection density and a strong downregulation of the corticoreticular projection density, with the noticeable exception in the latter case of a considerable increase of projection density following spinal cord injury, even enhanced when an anti-NogoA antibody treatment was administered. The effects were diverse and less prominent on the corticotectal and corticosubthalamic projections. The CS projection may still be the major efferent pathway through which motor adaptations can take place after motor trauma or disease. However, the parallel supraspinal motor corticofugal projections may also participate in connectional adaptations supporting the functional recovery of motor abilities, representing potential targets for future clinical strategies, such as selective electrical neurostimulations.