Chimeric antigen receptor (CAR) T‐cell therapy has dramatically shifted the landscape of treatment for lymphoid malignancies, especially diffuse large B‐cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL). However, there continue to be significant limitations of this therapy, such as incomplete or nonsustained responses and severe toxicities in a subset of patients. Furthermore, expanding the role of CAR T‐cell therapy to new disease types is an important next step. In this review, we will highlight landmark trials for anti‐CD19 CAR T cells and first‐in‐human trials of novel CARs, as well as discuss promising innovative CAR designs that are still undergoing preclinical development. Lastly, we will discuss toxicity and mechanisms of CAR T‐cell resistance and failure, as well as potential future treatment approaches to these common issues. - DOI: 10.1002/hon.2591 - 2019