Hypertensive disorders of pregnancy such as preeclampsia present an increasing source of concern during gestation and accumulating evidence suggests there are long-term effects on the subsequent health of the mother and child. While formerly preeclamptic women have increased risk for later cardiovascular disease, they appear to have decreased risk of some cancers. Recent investigations have revealed exciting insights into potential mechanisms underlying the pathogenesis of preeclampsia and some of these findings may bear relevance to the attenuated cancer risk reported in the literature. Placental ischemia, regarded as a primary initiating factor in preeclampsia, results in elevated levels of factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin/CD105 (sEng) that generate profound effects on the vascular endothelium and cardiovascular function, Further, these factors may also influence development of susceptible organs such as the mammary. Moreover, recent evidence suggests these molecules may be regulated by factors derived from cigarette smoke. Taken together, elucidating mechanisms linking placental ischemia, endothelial function and subsequent cancer risk is an important step towards identifying novel therapies for cancer.