Effective immunization induces the development of populations of robust effector lymphocytes specific for the immunizing antigens. Amongst them are cytotoxic/CD8(+)T lymphocytes, which few will further differentiate into long-lived memory cells persisting in the host and exhibiting improved functional characteristics. The current model is that such memory cells can confer rapid host protection upon cognate antigen-mediated activation and direct killing of infected cells. In this chapter, we discuss work from our group and others that highlight the contribution of inflammatory cytokines to memory CD8(+) T cell activation and of cytolysis-independent mechanisms of host protection.