One of the hallmarks of successful vaccination is the induction of strong and persistent memory T cell responses, a process that involves striking changes in the number and functional properties of T cells. Many questions pertaining to this complex, multifaceted process remain unanswered. Some of the key issues and challenges to optimize memory T cell responses and foster vaccine development include the optimization of effector T cell burst sizes, the use of adjuvants, cytokines and co-stimulatory molecules, epitope enhancement and the standardization of techniques to detect specific T cells. Age also has an impact on vaccine design because of the physiological changes in cell-mediated immunity that occur throughout life.