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Oncological surgery, obstetric haemorrhage and severe trauma are the most challenging conditions for establishing clinical recommendations for the use of cell salvage. When the likelihood of allogeneic transfusion is high, the intraoperative use of this blood-saving technique would be justified, but specific patient selection criteria are needed. The main concerns in the case of oncological surgery are the reinfusion of tumour cells, thereby increasing the risk of metastasis. This threat could be minimized, which may help to rationalize its indication. In severe peripartum haemorrhage, cell salvage has not proven cost-effective, damage control techniques have been developed, and, given the risk of fetomaternal alloimmunization and amniotic fluid embolism, it is increasingly out of use. In trauma, bleeding may originate from multiple sites, coagulopathy may develop, and it should be evaluated whether re-transfusion of autologous blood collected from uncontaminated organ cavities would be feasible. General safety measures include washing recovered blood and its passage through leukocyte depletion filters. To date, no well-defined indications for cell salvage have been established for these pathologies, but with accurate case selection and selective implementation, it could become safe and effective. Randomized clinical trials are urgently needed.