Chimeric antigen receptor (CAR)-T-cell therapy is a promising treatment for refractory malignancies but is associated with unique acute toxicities requiring specialized monitoring and management. The most common toxicities are cytokine-release syndrome (CRS) and CAR-T-cell-related encephalopathy syndrome (CRES). CRS can range from mild constitutional symptoms to life-threatening multiorgan dysfunction, while CRES typically presents with neurological symptoms such as confusion, delirium, and seizures. These toxicities can be managed with supportive care, anti-IL-6 therapy, and corticosteroids. The CARTOX Working Group has developed guidelines for the grading and management of these toxicities, which can also apply to other redirected-T-cell therapies. The guidelines emphasize the importance of early detection and intervention to minimize morbidity and mortality. The case study illustrates the management of a patient with refractory diffuse large-B-cell lymphoma who developed CRS and CRES following CAR-T-cell therapy. The patient was treated with tocilizumab for CRS and showed improvement. The guidelines recommend monitoring vital signs, laboratory tests, and neurological status, and using specific algorithms for grading and managing CRS, CRES, and HLH/MAS. Anti-IL-6 therapy is the first-line treatment for moderate-to-severe CRS, while corticosteroids are reserved for refractory cases. The use of corticosteroids is generally considered only when toxicities are refractory to anti-IL-6 therapy. The grading of CRES is based on neurological function, with a new 10-point neurological assessment tool (CARTOX-10) developed for this purpose. The guidelines also emphasize the importance of close monitoring and timely intervention to manage these toxicities effectively.Chimeric antigen receptor (CAR)-T-cell therapy is a promising treatment for refractory malignancies but is associated with unique acute toxicities requiring specialized monitoring and management. The most common toxicities are cytokine-release syndrome (CRS) and CAR-T-cell-related encephalopathy syndrome (CRES). CRS can range from mild constitutional symptoms to life-threatening multiorgan dysfunction, while CRES typically presents with neurological symptoms such as confusion, delirium, and seizures. These toxicities can be managed with supportive care, anti-IL-6 therapy, and corticosteroids. The CARTOX Working Group has developed guidelines for the grading and management of these toxicities, which can also apply to other redirected-T-cell therapies. The guidelines emphasize the importance of early detection and intervention to minimize morbidity and mortality. The case study illustrates the management of a patient with refractory diffuse large-B-cell lymphoma who developed CRS and CRES following CAR-T-cell therapy. The patient was treated with tocilizumab for CRS and showed improvement. The guidelines recommend monitoring vital signs, laboratory tests, and neurological status, and using specific algorithms for grading and managing CRS, CRES, and HLH/MAS. Anti-IL-6 therapy is the first-line treatment for moderate-to-severe CRS, while corticosteroids are reserved for refractory cases. The use of corticosteroids is generally considered only when toxicities are refractory to anti-IL-6 therapy. The grading of CRES is based on neurological function, with a new 10-point neurological assessment tool (CARTOX-10) developed for this purpose. The guidelines also emphasize the importance of close monitoring and timely intervention to manage these toxicities effectively.