During neuronal development, neurotrophins are essential factors that promote survival, differentiation and myelination of neurons. The trophic signals are relayed to the cells via binding to Trk receptor tyrosine kinases and the p75 neurotrophin receptor. Paradoxically, the p75 neurotrophin receptor also ensures rapid and appropriate apoptosis of neonatal neurons not reaching their proper targets and transmits death signals to injured neurons. Until recently, the mechanisms by which the p75 neurotrophin receptor governs these opposing functions have remained elusive. By the identification of new ligands and cytosolic interacting partners, receptor cleavage products and coreceptors, some of these mechanisms are now being unraveled. Here, we review recent progress in delineating the molecular networks that enable p75(NTR) to dictate life and death.