The neurotrophins utilize a complex receptor system consisting of Trk receptor tyrosine kinases and the structurally unrelated tumor necrosis factor receptor family member, p75(NTR), to confer diverse and sometimes opposing biological actions. The recent identification of selective ligands for p75(NTR), novel isoforms of this receptor, as well as new signaling partners, suggest that the numerous biological actions of the neurotrophins via p75(NTR) may reflect selectivity of ligand-receptor interactions and intracellular adaptor protein recruitment.