Chimeric antigen receptors (CARs) are synthetic proteins designed to direct an immune response toward a specific target and have been used in immunotherapeutic applications through the adoptive transfer of T cells genetically engineered to express CARs. This technology received early attention in oncology with particular success in treatment of B cell malignancies leading to the launch of numerous successful clinical trials and the US Food and Drug Administration approval of several CAR-T-based therapies. Many CAR-T constructs have been employed, but have always been administered following a lymphodepletion regimen. The success of CAR-T cell treatment in targeting malignant B cells has led many to consider the potential for using these regimens to delete pathogenic B cells in autoimmune diseases. Preliminary results have suggested efficacy, but the sample size remains small, controlled trials have not been done, the role of immunodepletion has not been established, the most effective CAR-T constructs have not been identified and the most appropriate patient subsets for treatment have not been established.