The specialized architecture of neurons necessitates unique modes of intracellular communication to allow for cell survival, the ability to detect and respond to injury and aspects of neuronal development, such as axon and dendrite growth, plasticity, and synapse and circuit formation. Many of these neuronal processes rely on signal transduction pathways and transcriptional programmes that are activated by retrograde signals originating from target-derived cues that act on distal axons. Here, we review the many functions of long-range distal axon-to-cell body signalling and discuss mechanisms of retrograde target-derived growth factor signalling.