The nerve transection model is an established and validated experimental model of skeletal muscle atrophy prepared by denervating the skeletal muscle in rodents. While a number of denervation techniques are available in rats, the development of various transgenic and knockout mice has also led to the wide use of mouse models of nerve transection. Skeletal muscle denervation experiments expand our knowledge of the physiological role of nerval activity and/or neurotrophic factors in the plasticity of skeletal muscle. The denervation of the sciatic or tibial nerve is a common experimental procedure in mice and rats, as these nerves can be resected without great difficulty. An increasing number of reports have recently been published on experiments using a tibial nerve transection technique in mice. In this chapter, we demonstrate and explain the procedures used to transect the sciatic and tibial nerves in mice.