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 pregnancy-associated 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 life-threatening 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.