Chimeric antigen receptor (CAR) T-cell therapy is a recently approved breakthrough treatment that has become a new paradigm in treatment of recurrent or refractory B-cell lymphomas and pediatric or adult acute lymphoid leukemia. CAR T cells are a type of cellular immunotherapy that artificially enhances T cells to boost eradication of malignancy through activation of the native immune system. The CAR construct is a synthetically created functional cell receptor grafted onto previously harvested patient T cells, which bind to preselected tumor-associated antigens and thereby activate host immune signaling cascades to attack tumor cells. Advantages include a single treatment episode of 2-3 weeks and durable disease elimination, with remission rates of over 80%. Responses to therapy are more rapid than with conventional chemotherapy or immunotherapy, with intervening short-interval edema. CAR T-cell administration is associated with therapy-related toxic effects in a large percentage of patients, notably cytokine release syndrome, immune effect cell-associated neurotoxicity syndrome, and infections related to immunosuppression. Knowledge of the expected evolution of therapy response and potential adverse events in CAR T-cell therapy and correlation with the timeline of treatment are important to optimize patient care. Some toxic effects are radiologically evident, and familiarity with their imaging spectrum is key to avoiding misinterpretation. Other clinical toxic effects may be occult at imaging and are diagnosed on the basis of clinical assessment. Future directions for CAR T-cell therapy include new indications and expanded tumor targets, along with novel ways to capture T-cell activation with imaging. An invited commentary by Ramaiya and Smith is available online. Online supplemental material is available for this article. ©RSNA, 2022.