The anamnestic response is the property of the immune system that makes vaccine development possible. Although the development of a vaccine against Mycobacterium tuberculosis is an important global priority, there are many gaps in our understanding of how immunological memory develops following M. tuberculosis infection or after BCG vaccination. In experiments designed to compare the anamnestic response of susceptible and resistant mouse strains, major histocompatibility complex-matched memory-immune C3.SW-H2(b)/SnJ and C57BL/6 mice both demonstrated better control of bacterial replication following reinfection with M. tuberculosis than control mice. Nevertheless, this memory response did not appear to have any long-term protective effect for either mouse strain. A greater understanding of the immunological factors that govern the maintenance of immunological memory following exposure to M. tuberculosis will be required to develop an effective vaccine.