OBJECTIVES: To describe the most common serious adverse effects and organ toxicities associated with emerging therapies for cancer that may necessitate admission to the ICU. DATA SOURCES AND STUDY SELECTION: PubMed and Medline search of relevant articles in English on the management of adverse effects of immunotherapy for cancer. DATA EXTRACTION AND DATA SYNTHESIS: Targeted therapies including tyrosine kinase inhibitors, monoclonal antibodies, checkpoint inhibitors, and immune effector cell therapy have improved the outcome and quality of life of patients with cancer. However, severe and life-threatening side effects can occur. These toxicities include infusion or hypersensitivity reactions, cytokine release syndrome, pulmonary, cardiac, renal, hepatic, and neurologic toxicities, hemophagocytic lymphohistiocytosis, opportunistic infections, and endocrinopathies. Cytokine release syndrome is the most common serious toxicity after administration of monoclonal antibodies and immune effector cell therapies. Most of the adverse events from immunotherapy results from an exaggerated T-cell response directed against normal tissue, resulting in the generation of high levels of proinflammatory cytokines. Toxicities from targeted therapies are usually secondary to "on target toxicities." Management is largely supportive and may include discontinuation of the specific agent, corticosteroids, and other immune suppressing agents for severe (grade 3 or 4) immune-related adverse events like neurotoxicity and pneumonitis. CONCLUSIONS: The complexity of toxicities associated with modern targeted and immunotherapeutic agents for cancer require a multidisciplinary approach among ICU staff, oncologists, and organ specialists and adoption of standardized treatment protocols to ensure the best possible patient outcomes.