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The unprecedented success of chimeric antigen receptor (CAR)-T-cell therapy in the management of B-cell malignancies comes with a price of specific side effects. Healthy B-cell depletion is an anticipated 'on-target' 'off-tumor' side effect and can contribute to severe and prolonged hypogammaglobulinemia. Evidence-based guidelines for the use of immunoglobulin replacement therapy (IGRT) for infection prevention are lacking in this population.This article reviews the mechanisms and epidemiology of hypogammaglobulinemia and antibody deficiency, association with infections, and strategies to address these issues in CD19- and BCMA-CAR-T-cell recipients.CD19 and BCMA CAR-T-cell therapy result in unique immune deficits due to depletion of specific B-lineage cells and may require different infection prevention strategies. Hypogammaglobulinemia before and after CAR-T-cell therapy is frequent, but data on the efficacy and cost-effectiveness of IGRT are lacking. Monthly IGRT should be prioritized for patients with severe or recurrent bacterial infections. IGRT may be more broadly necessary to prevent infections in BCMA-CAR-T-cell recipients and children with severe hypogammaglobulinemia irrespective of infection history. Vaccinations are indicated to augment humoral immunity and can be immunogenic despite cytopenias; re-vaccination(s) may be required. Controlled trials are needed to better understand the role of IGRT and vaccines in this population.