Pregnancy-associated high-risk pulmonary embolism (PE) is among the most frequent causes of maternal mortality in the Western world, by causing hemodynamic instability and circulatory failure through a large thrombotic pulmonary obstruction. The very challenging management of these dramatic situations comprises the need to quickly select a therapy of pulmonary reperfusion or hemodynamic replacement, while taking into account both maternal and fetal risks. In this review, we discuss the role of risk stratification in pregnancyassociated PE and the available evidence to support the use of thrombolysis, catheter-directed thrombectomy/ thrombolysis, surgical embolectomy and extracorporeal membrane oxygenation. Despite the lack of comparative studies and solid evidence, most reported cases of high-risk pregnancy-associated PE have been treated with thrombolysis, with high maternal and fetal survivals, and thrombolysis is suggested by guidelines in lifethreatening PE. For women in the peripartum and early post-partum period, non-fibrinolytic treatments may be preferred as a first-line treatment, if available, because of the particularly high bleeding risk. In all cases, pregnancy-associated high-risk PE requires a multidisciplinary approach involving PE response teams and obstetricians.