INTRODUCTION: The last few years have witnessed what can certainly be defined as a 'period of renaissance' for immunotherapy in the field of hematological malignancies. In particular, antibody-mediated and cell-mediated immunotherapy have significantly changed the treatment approach of patients with B-cell lymphoproliferative disorders. These therapies, initially employed in patients with refractory/relapsed disease, are now integrated in the treatment of newly diagnosed patients. Together with the therapeutic success, we have also learnt that these innovative therapies can induce relevant, sometimes life-threatening or even fatal, side effects. Areas covered: In this review article, we analyzed the applicative therapeutic scenario and the peculiar toxicities associated with approaches of immunotherapy, paying particular attention to the new emerging side effects, substantially unknown before the introduction of these therapies. Expert commentary: Both monoclonal antibodies and cell therapy with lymphocytes genetically modified to be redirected against leukemia targets through the transduction with chimeric antigen receptors (CARs) have obtained unprecedented success in rescuing patients with resistant B-cell malignancies. Complications, such as neurotoxicity, cytokine release syndrome or persistent B-cell lymphopenia, must always be taken into consideration and diagnosed in a timely manner in patients with B-cell neoplasms to guarantee optimal management, thus avoiding they blunting the efficacy of immunotherapy.