Gestational-hypertension/pre-eclampsia occurs in approximately 10% of human pregnancies. This persistent complication of pregnancy has been reported to occur more frequently in couples conceiving very shortly after the beginning of their sexual relationship and/or after a change in paternity. Primipaternity may be the leading cause of pre-eclampsia in women under 30 years of age when genetic susceptibility to cardio-vascular disease has not yet been expressed, especially in women before their twenties, who for the last 40,000 years have perhaps comprised the age group when the majority of parturients classified as Homo sapiens sapiens initiated their reproductive life. In terms of evolution, the prevalence of pre-eclampsia represents a distinct reproductive disadvantage in humans as compared with other mammals. Indeed, pre-eclampsia is a consequence of the defect of the normal human-specific deep endovascular invasion of the trophoblast. The large size of the human fetal brain imposing this deep trophoblastic invasion induced the need for major immunogenetic compromises in terms of paternal–maternal tissue tolerance. The price that mankind has had to pay to adapt to the pre-eclampsia risk is a low fecundability rate and therefore loss of oestrus, possibly a step in the deviation between apes and hominids. Further, pre-eclampsia risk may be a contributing factor leading to the rejection of systematic polyandry in human societies and have influenced prohibition of incest.