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Targeted therapies, molecules in full expansion, are not free of side effects that can lead patients to intensive care. We performed an extensive review of the published evidence and propose a management strategy for acute complications of targeted therapy in critically ill patients with cancer.The literature search was performed in August 2017 using the Ovid Medline system by a scientific librarian and physicians. We made a review of cases admitted in intensive care unit (ICU) and a review of toxicities of grades greater or equal to 3.Our search selected 59 articles. The main cardiovascular side effects requiring ICU are heart failure, which is generally reversible, severe hypertension, thrombotic and ischemic events, and rhythm disturbances. The main pulmonary side effects are interstitial lung disease essentially caused by crizotinib, respiratory infections, pneumothorax, and alveolar hemorrhage. The main gastrointestinal side effects are fulminant hepatitis that may be fatal, colitis that may be complicated by hemorrhage, and perforation. The main neurological side effect is posterior reversible encephalopathy syndrome essentially caused by bevacizumab. The main other side effects are Steven-Johnson syndrome, necrotizing fasciitis, and anaphylactic reactions.The side effects induced by targeted therapies may be fatal but are generally potentially reversible. The main treatment includes stopping current therapy and symptomatic management. Treatment rechallenge should be discussed on a case-by-case basis.