Age is the most prominent factor for survival in all patients diagnosed with lymphoma, and male sex implies an increased and independent risk for a worse progression-free survival (PFS) and overall survival (OS) in most lymphomas, possibly with the exception of mantle cell lymphoma (MCL). The worse outcome for elderly patients is only partially explained by decreased tolerance to treatment regimens associated with the increasing number and severity of comorbidities. Little is known about specific differences in lymphoma biology with respect to age and sex, and this is changing only slowly despite the recent rise in interest about these issues. To better understand the differences and their underlying mechanisms, questions of age- and sex-specific outcomes, their correlation with pharmacokinetic data, and planned and received doses, must be addressed and reported in prospective clinical trials. Such studies must be accompanied by translational research that investigates biologic differences of lymphomas between old and young and male and female patients by addressing the microenvironment, cytogenetics including next-generation sequencing and systems biology of lymphomas, and correlation of these findings with treatment results. This knowledge will enable us to adjust lymphoma treatment to the necessities of more personalized medicine.