During development, targets of outgrowing axons produce neurotrophins. These signaling molecules exert short-distance effects on neuronal growth cones as well as long-distance effects on neuronal cell bodies and nuclei. The retrograde signaling from axon tips to cell bodies is essential for the regulation of neuronal survival during the period of naturally occurring programmed cell death in the nervous system. During this time window, neurons that fail to establish appropriate connections with their target tissues are eliminated by apoptosis. Neurotrophins (nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5) may influence neuronal survival not only via signaling through Trk receptors but also through interactions with p75NTR. Retrograde transport of neurotrophins and their receptors within organelles coined ‘signaling endosomes’ is one potential mechanism contributing to retrograde signaling. However, alternative pathways not involving retrograde transport of neurotrophins are emerging. The current models of retrograde neurotrophin signaling from synapses to cell bodies are discussed, with special focus on potential roles of the enigmatic p75NTR receptor in neurotrophin trafficking.