The incidence of diffuse large B-cell lymphoma (DLCL) in the older is growing to the point of becoming a health priority in the next decades. Prognostic factors and the biology of the tumor are not very different between younger and older populations. Furthermore, it seems that the response rate is basically similar in both populations, provided an appropriate dose of chemotherapy is administered. However, there seem to be differences with regard to a lower tolerance to treatment and a higher relapse rate in responsive older patients. To analyze these problems we review the most important differences between young and older DLCL patients in terms of immunologic status, treatment toxicity and the presence of other concomitant diseases or organ dysfunctions. We also consider the most relevant clinical studies that may allow us to make the appropriate decisions regarding DLCL therapy in this older population.