Older patients with diffuse large B-cell lymphoma (DLBCL) represent a particularly challenging population. Reduced-dose rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-miniCHOP) can cure approximately half of patients; however, those who fail frontline therapy or are ineligible for anthracycline-based regimens have historically been considered to have a dismal prognosis. Nevertheless, over the past few years, several effective salvage immunotherapies have been introduced into clinical practice, including naked monoclonal antibodies, such as tafasitamab, antibody–drug conjugates, such as polatuzumab vedotin, and loncastuximab tesirine, and CD20 × CD3 bispecific antibodies (BsAbs). Moreover, novel combined approaches are currently under investigation as frontline therapy, such as the triplets polatuzumab vedotin plus rituximab and glofitamab (Pola-R-Glo), and tafasitamab plus lenalidomide and rituximab (TLR), or the upfront use of single-agent CD20 × CD3 BsAbs. These strategies aim to spare toxicity in older and frail patients and have shown promising efficacy, potentially heralding a chemo-free era for DLBCL in the older in the near future.