BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is an adoptive cellular immunotherapy that is being utilized more frequently due to its initial success in advanced-stage cancers. Unfortunately, CAR T-cell therapy is often associated with acute systemic toxicities, including cytokine release syndrome (CRS) and CAR T-cell-associated neurotoxicity (neurotoxicity). OBJECTIVE: We created a review that addresses the potential common emergency department (ED) presentations associated with CAR T-cell therapy. We reviewed the relevant research and clinical guidelines to develop a guide tailored toward addressing the needs of the emergency medicine community to manage these complications. In addition, a case is presented and the evaluation and management of CRS and neurotoxicity are reviewed in detail. DISCUSSION: Despite CAR T-cell designs showing promising results, the risk of acquiring an acute toxicity is high, with CRS and neurotoxicity reported most often. The systemic toxicities associated with these adverse events can lead to end-organ damage and compromise the patient acutely or jeopardize the continuation in treatment of their underlying malignancy. Depending on the severity of the toxicity, treatment typically starts with vigilant supportive care, but may include administration of tocilizumab and possibly high-dose corticosteroids if the toxicity is deemed of high severity. CONCLUSIONS: With the increasing administration of CAR T-cell therapy, emergency physicians will likely encounter more patients with associated adverse events, including CRS and neurotoxicity. It is increasingly important that emergency physicians are aware of these potential toxicities in order to rapidly diagnose and treat patients undergoing CAR T-cell therapy.