At vanishingly low concentrations, factors of the neurotrophin family (NGF, BDNF, NT3 and NT4/5) can promote neuronal survival or death. Many investigations indicate that the survival-promoting signals of neurotrophins are generated by activation of Trk tyrosine kinase receptors and that their death-promoting signals are generated by activation of p75 neurotrophin receptors (p75(NTR)). Despite this, a body of work indicates that p75(NTR) can promote cell survival and Trk receptors can adversely affect neuron health. The potential mechanisms by which these receptors could have such diverse and antipodal effects are considered here.