Preeclampsia is a systemic disease that results from placental defects and occurs in about 5–8% of pregnancies worldwide. Preeclampsia is a disease of many theories, wherein investigators put forward their favorite mechanistic ideas, each with a causal appeal for the pathogenesis of preeclampsia. In reality, the patho-mechanism of preeclampsia remains largely unknown. Preeclampsia, as diagnosed in patients today, is likely a heterogeneous collection of disease entities that share some common features but also show important differences. Therefore, one single mechanism may never be found to explain all the variants of preeclampsia. Current research must focus on evaluating such diverse mechanisms, as well as the possible common effector pathways. Here, we provide a discussion of several possible mechanisms and putative theories proposed for preeclampsia, with particular emphasis on the recent discovery of a new genetic mouse model offering new opportunities to explore experimental therapies.