Preeclampsia is a pregnancy-specific complex disease in which numerous genetic, immunological and environmental factors interact. Characterized by new onset hypertension, proteinuria and edema after 20 weeks of gestation, preeclampsia is often complicated by small-for-gestational-age (SGA) babies and pre-term delivery, and is therefore a significant cause of maternal and fetal morbidity and mortality. The only definitive treatment of preeclampsia is delivery of the placenta. Recent data suggest that the anti-angiogenic state induced by excess circulating anti-angiogenic factors of placental origin may be responsible for the clinical signs and symptoms of preeclampsia. Natural killer (NK) cells at the maternal/fetal interface, which are thought to play an important role in normal placental development, have been noted recently to induce angiogenic factors and vascular remodeling. Moreover, genetic studies suggest that susceptibility to preeclampsia may be influenced by polymorphic HLA-C ligands and killer cell receptors (KIR) present on NK cells. This review summarizes our current understanding of the role of angiogenic factors and NK cells in the pathogenesis of preeclampsia.