Axonal transection provides very useful paradigms to study cellular re
sponses to injury, mechanisms of regeneration and plasticity, and proc
esses that lead to nerve cell degeneration. Moreover, models of axotom
y are valuable for testing experimental therapeutic approaches. Lesion
s can be made with great precision, and, depending on the neural syste
m, location of the lesion, and age of the animal, these models allow t
he opportunity to examine a range of neuronal responses. Many paramete
rs influence the character, evolution, and outcomes of axotomy-related
processes. The most severe outcome of axotomy is cell death, very com
mon in lesions of neurons of the central nervous system (CNS), althoug
h neurons of the peripheral nervous system (PNS) may also die if the t
ransection is sufficiently close to the neuronal cell body or if lesio
ns are performed in young animals. Studies of axotomy models have prov
ided clues into the cellular/molecular events associated with neuronal
death and the ways in which interventions can delay or prevent proces
ses that lead to cell death. In this review, we select examples, prima
rily from our own work, to illustrate how axotomy models have enhanced
our understanding of neuronal responses to injury, clarified mechanis
ms of both regeneration/plasticity and degeneration/cell death, and al
lowed assessments of the utility of therapeutic approaches.