Motoneurones are known to die (1) during embryonic development (naturally occurring cell death), (2) early in postnal development after axonal injury, and (3) as a consequence of disease such as SMA. Interactions with the target emerges as an important factor for survival of developing montoneurones. The evidence for the target dependence od of developing motoneurones will be presented and the mechanisms by which the muscle may regulate motoneurone survival discussed. Results that argue for the following proposal will be given: with maturation of the CNS motor activity in all mammals increases as do the functional demands on the motoneurones. The target muscle's role is to induce changes in the motoneurone to make it competent to respond to increased amounts of glutamate from excitatory inputs and thus allow it to carry out the tasks associated with its increased activity. A failure of the muscle to induce these changes in the motonerone's phenotype in time may lead to motoneurone death. In addition new approaches that could (1) improve motoneurone survival, and (2) use embryonic grafts to replace the lost cells will be discussed.