Neurotrophins are a group of secreted polypeptides, which comprises Nerve Growth Factor (NGF) and Brain‐Derived Neurotrophic Factor (BDNF). Each neurotrophin can bind specifically to a tyrosine kinase Trk receptor (TrkA, TrkB or TrkC), while all of the neurotrophins can bind, with similar affinity, to the p75 neurotrophin receptor (p75NTR). Experiments on cell viability promotion by BDNF in granule neurons or by NGF in PC12 cells show that neurotrophin‐exerted cell viability is neutral sphingomyelinase (nSMase)‐dependent, since GW4869 or siRNA knockdown abrogates the protective effects, as well as neurotrophin‐induced Akt phosphorylation. Finally, the assessment of nSMase activity promotion drives to the conclusion that neurotrophins can promote cell viability through Trk receptors in a manner depending on basal nSMase but not through SMase activity enhancement.