Men and women not only look different, but they have different risks of multiple diseases like migraine, neurodegenerative disorders or numerous cancers. Even the nerve cells may die in different ways and exhibit different sensitivity to pro-apoptotic factors. Some of the differences can be explained by the action of sex hormones, but the experiments on four core genotype mouse model, in which XX and XY mice can be of either sex showed that not all differences are due to hormones. An example of a disease with no simple explanation of sex bias is Leber hereditary optic neuropathy, a mitochondrial disease with about 4:1 male to female ratio. The apoptotic death of retinal ganglion cells forming an optic disc is a proposed mechanism of the disease pathophysiology. The mechanisms causing different sensitivity of the nerve cells of male and female subjects may be responsible for the gender bias in LHON and merit further studies.