Pre-eclampsia is the second leading cause of maternal morbidity and mortality in the United States. Infants born to affected mothers face a five-fold increase in death rate [Lain and Roberts 2002; National Heart Lung and Blood Institute 2001]. Although pre-eclampsia has been recognized by physicians for millennia, relatively little is known about its pathogenesis or prevention. Predicting its development is often extremely difficult, perhaps leading the Greeks to use the name 'eklampsis' meaning lightening. Recent studies provide novel insights into the role of the placenta in the development of pre-eclampsia and demonstrate novel markers to assist in predicting the onset of disease and potential therapeutic targets. Following an introduction which highlights the classification of hypertensive disorders of pregnancy and defines incidence and adverse outcomes of pre-eclampsia, this manuscript will discuss the role of the placenta in the pathophysiology of pre-eclampsia and recent markers that may predict its onset.