OBJECTIVES Preeclampsia complicates 5-8% of all pregnancies and remains a leading cause of maternal and perinatal morbidity and mortality. Negative outcomes could be avoided in many patients if a reliable early diagnostic test were available. We systematically reviewed the literature to assess the current status of development of early diagnostic tests for preeclampsia. METHODS We searched English-language MEDLINE-indexed publications in the 10 years prior to August 2008 concerning tests for early diagnosis of preeclampsia, and literature published in the 5 years prior to August 2008 using keywords relating to biomarkers for preeclampsia. We also searched non-MEDLINE-indexed sources such as organization websites, meeting abstracts, and governmental publications using the same keywords. RESULTS We identified 116 primary studies from MEDLINE pertaining to biomarkers or tests for early diagnosis of preeclampsia. Non-MEDLINE sources yielded an additional 2 articles for a total of 118 reviewed for this study. A variety of serum biomarkers have been explored as candidates for predictive diagnostic tests for preeclampsia. These biomarkers represent a number of pathological processes involved in preeclampsia, including endothelial damage, oxidative stress, altered lipid and glucose metabolism, inflammation, and abnormal immune responses. The angiogenesis-related biomarkers PlGF and sFlt-1 are at the most advanced state of development as diagnostic tests, with PlGF decreases and sFlt-1 increases preceding overt clinical symptoms by 5-10+ weeks. PlGF has potential to allow screening as early as 14 weeks of gestation, and sFlt-1 by week 16. Further research is needed to determine whether change in these biomarkers predicts preeclampsia or indicates substantially increased risk, or conversely, whether lack of change precludes preeclampsia or indicates lower risk. CONCLUSIONS Currently, the angiogenesis-related biomarkers PlGF and sFlt-1 offer the most promise for use in the early diagnosis of preeclampsia.