Despite decades of intense research on the problem, pre-eclampsia remains one of the great mysteries of medical science. This paper is an overview of the existing knowledge on the disease that unifies the essential and validated findings of past and current scientific investigation. A key focus has been an attempt to distinguish foundationally pathogenic mechanisms from multiple epiphenomena that continue to be elucidated. The hypothesis was developed after taking into consideration the various known risk factors for pre-eclampsia, epidemiologic trends, and the most available research to date regarding the pathogenesis of the disease. In summary, it may be stated that pre-eclampsia is a systemic disease of maternal endothelial cell dysfunction, resulting from a deficient endovascular invasion of fetal extravillous cytotrophoblasts into the maternal spiral arterioles--a process facilitated by cytokine and angiogenic factor producing uterine/decidual CD56bright Natural Killer (NK) cells and impeded by the more cytotoxic peripheral CD56dim NK cells of the innate immune system. Therefore, the disease process appears to be fundamentally one of a unique variant of immune maladaptation at the level of the maternal-fetal interface in the setting of more or less susceptible persons caused by a mixture of both insufficient maternal tolerance induction to the paternal antigens and unfavourable combinations of genetically determined maternal leukocyte receptors and fetal antigens.