Lower vertebrates, such as fish and amphibians, and developing higher vertebrates can regenerate complex body structures, including significant portions of their central nervous system. It is still poorly understood why this potential is lost with evolution and development and becomes very limited in adult mammals. In this review, we will discuss the current knowledge on the cellular and molecular changes after spinal cord injury in adult tailed amphibians, where regeneration does take place, and in developing chick and mammalian embryos at different developmental stages. We will focus on the recruitment of progenitor cells to repair the damage and discuss possible roles of changes in early response to injury, such as cell death by apoptosis, and of myelin-associated proteins, such as Nogo, in the transition between regeneration-competent and regeneration-incompetent stages of development. A better understanding of the mechanisms underlying spontaneous regeneration of the spinal cord in vivo in amphibians and in the chick embryo will help to devise strategies for restoring function to damaged or diseased nervous tissues in mammals.