In the course of an immune response to an infectious microbe, pathogen-specific naïve CD4⁺ T cells proliferate extensively and differentiate into effector cells. Most of these cells die rapidly, but a small fraction of effector cells persist as memory cells to confer enhanced protection against the same pathogen. Recent advances indicate that strong TCR stimulation during the primary response is essential for the generation of long-lived memory CD4⁺ T cells. Memory cells appear to be derived equally from all subsets of effector cells, and memory cells can also acquire additional functional capabilities during the secondary response. Resting memory CD4⁺ cells are dependent on signals from contact with IL-7 and IL-15, but not MHC class II, for their survival and intermittent homeostatic proliferation.