Severe bleeding remains a leading cause of morbidity and mortality in obstetrics. The first-line standard treatment of massive postpartum hemorrhage (PPH) includes medical measures directed at improving uterine tone, replacement of lost intravascular volume, blood and coagulation factors, and surgical or invasive procedures. Recently, a number of case reports or case series have reported the successful “off-label” use of recombinant activated factor VII (rFVIIa) in PPH unresponsive to conventional treatments. In this review, a critical analysis of the published literature on the use of rFVIIa in severe PPH was performed. Overall, a total of 272 PPH women were collected among the largest case series and/or international registries. No randomized controlled trials have been conducted in this area. Currently, the literature data suggest that, at a median dose of 81.5 μg/kg, rFVIIa is effective in stopping or reducing bleeding in 85% of the cases. Finally, on the basis of the evidence from the literature and on own experience, we included some recommendations and an algorithm on the therapeutic role of rFVIIa in the management of PPH.