Alzheimer's disease is characterized by the over-production and accumulation of amyloidogenic Aβ peptide, which can induce cell death in vitro. It has been suggested that the death signal could be transduced by the pan neurotrophin receptor (p75NTR). p75NTR is well known for its ability to mediate neuronal death in neurodegenerative conditions and is inextricably linked with changes that occur in Alzheimer's disease. Moreover, Aβ binds to p75NTR, activating signalling cascades. However, the complexity of p75NTR-mediated signalling, which does not always promote cell death, leaves open the possibly of Aβ promoting death via an alternative signalling pathway or the regulation of other p75NTR-mediated actions. This review focuses on the interactions between Aβ and p75NTR in the context of the broader p75NTR signalling field, and offers alternative explanations for how p75NTR might contribute to the aetiology of Alzheimer's disease.