The role of the target in the survival of developing motoneurones is discussed. The contribution of neurotrophic factors is re-evaluated in view of the following: (1) motoneurone numbers are affected only slightly in transgenic mice following deletions of genes coding for neurotrophins or their receptors; and (2) continued treatment with neurotrophins fails to achieve long-term motoneurone survival. Evidence that motoneurone survival depends on the induction of transmitter release initiated by contact between nerve and muscle is presented. The release of transmitter and the ensuing retraction of many axon branches transforms the motoneurone from a growing cell into a transmitting cell. It is suggested that only when motoneurones have undergone this transition can they survive within the mature CNS.