Hypertensive disorders of pregnancy (HDP) represent globally 10% of human births and their major complication, preeclampsia, 3 to 5%. The aetiology of these HDP remains still uncertain, however major advances have been made these last 25 years. The defect of trophoblastic invasion encountered in preeclampsia, intra-uterine growth restriction and to some extent also preterm labour has been understood only at the end of the 1970’s. On the other hand, clinical and epidemiological findings at the end of the 20th century permitted us to apprehend that “preeclampsia disease of primiparae” may in fact well be the disease of first pregnancies at the level of human couples. Among the important advances, immunology of reproduction is certainly the topic where knowledge has literally exploded in the last decade. This paper relates some major steps in comprehension of this disease and provides a review of epidemiological studies on the “primipaternity paradigm”. It focuses therefore on the interest to follow these immunological works and their new concepts. It seems, at the beginning of the 21st century, that we are possibly closer than ever to understand the aetiology of this obstetrical enigma and also the pathophysiology of the global endothelial inflammation in preeclamptic women. In this quest, the immunology of reproduction will certainly come out as one of the main players.