Chimeric antigen receptor T-cell (CAR-T) therapy has improved outcomes in patients with relapsed/refractory hematological malignancies. Research is also extending to other diseases, including solid tumors, infections and autoimmune disorders. As living drugs, CAR-T cells are associated with potentially life-threatening immunological toxicities, which frequently require a multidisciplinary team approach. Cytokine-release syndrome, immune effector cell-associated neurotoxicity syndrome, infections and hematotoxicity (including cytopenias, immune reconstitution dysfunction and hypogammaglobulinemia) are associated with significant morbidity and mortality. This review takes a practical approach to summarize current knowledge on CAR-T toxicity, addressing pathogeny, risk factors, and prophylactic and therapeutic strategies.