The success of pregnancy is a result of countless ongoing interactions between the placenta and the maternal immune and cardiovascular systems. Pre-eclampsia is a serious pregnancy complication that arises from multiple potential aberrations in these systems. The pathophysiology of pre-eclampsia is established in the first trimester of pregnancy, when a range of deficiencies in placentation affect the key process of spiral artery remodelling. As pregnancy progresses to the third trimester, inadequate spiral artery remodelling along with multiple haemodynamic, placental and maternal factors converge to activate the maternal immune and cardiovascular systems, events which may in part result from increased shedding of placental debris. As we understand more about the pathophysiology of pre-eclampsia, it is becoming clear that the development of early- and late-onset pre-eclampsia, as well as intrauterine growth restriction (IUGR), does not necessarily arise from the same underlying pathology.