Recent studies suggest that memory T-cell differentiation continues for weeks or months following antigen clearance, although commitment to the memory lineage occurs during the effector stage of development. Several variables associated with priming, such as the duration of antigenic stimulation, degree of co-stimulation, cytokine environment, and CD4(+) T-cell help, may program epigenetic qualitative differences into the ensuing effector and memory populations. Defining what memory qualities best protect the organism from re-infection, as well as how commitment to the memory lineage is specified following T-cell activation remains an important goal.