Most patients with diffuse large B-cell lymphoma (DLBCL) are >65 years of age, with the number of patients expected to increase in the coming years. A comprehensive geriatric assessment that carefully evaluates fitness status and comorbidities is essential for selecting the appropriate treatment intensity. Although generally healthy patients or those <80 years of age may benefit from standard immunochemotherapy, unfit/frail patients or patients >80 years old may require reduced-intensity chemotherapy or less-toxic drugs. Some new drugs are currently being tested as single or combined agents for first-line treatment, aiming to improve the outcomes of conventional chemotherapy. This review systematically collates and discusses the outcomes associated with the use of immunochemotherapy in older patients with DLBCL, as well as considering the impact of full-dose immunochemotherapy on quality of life in older and frail patients, summarizing the rationale for reduced dosing in the older population, and presenting recommendations for selecting patients likely to benefit from reduced dosing. If preliminary efficacy and safety data are confirmed in future clinical trials, non-chemotherapy-based immunotherapy approaches could become an alternative potentially curative option in frail patients and those >80 years of age with DLBCL.