In this treatise, current knowledge on the neurogenesis, axonal outgrowth, synaptogenesis, and regenerative capacity of descending supraspinal pathways in tetrapods is discussed. Although emphasis is on the clawed toad, Xenopus laevis, chicken embryos, opossums and rodent data, also the data available for primates including man are presented. It will be shown that 1) the outgrowth of descending supraspinal pathways is the result of a coordinated program; 2) the pattern of early descending axonal tracts is similar in all vertebrate groups; 3) the formation of descending supraspinal pathways occurs according to a developmental sequence; 4) the earliest descending supraspinal fibers arrive in a rather immature spinal cord, and 5) the regenerative capacity of descending supraspinal pathways depends on the developmental stage the particular pathways arise.