The diagnosis of chronic villitis of unknown etiology (CVUE), characterized by focal areas of inflammation with mononuclear cells and areas of fibrinoid necrosis in chorionic villi, can only be set-up after exclusion of a latent maternal-fetal transmission of infectious agents by sophisticated techniques such as polymerase chain reaction. Significant associations of CVUE with maternal body mass index, multigravidity and ethnicity were reported. While a fetal origin of the inflammatory cells has been evoked, there are many more arguments drawn from histopathology and immunohistology for a maternal immune response against the foreign fetal allograft. CVUE is detected in 7-33% of placentas, mainly after idiopathic intrauterine growth retardation, unexplained prematurity, preeclampsia, perinatal asphyxia and intrauterine fetal death. CVUE is also more frequent in pregnancies affected by autoimmune or alloimmune diseases. Considering the high rate of recurrences after an index case of CVUE, we would suggest to associate aspirine and corticosteroids in further pregnancies, a regimen that was successful in our experience but must be confirmed by other studies. The same is true for the alleviated inflammatory immunologic response recently obtained by a weekly use of maternal intravenous immunoglobulins.