CD4 T-cell memory is in some ways more enigmatic than CD8 T-cell memory. This is mostly due to the fact that CD4 T cells tend to expand far less in response to antigenic stimuli, thereby thwarting attempts at their detection during the course of an immune response. Nevertheless, there is a wide range of experimental models that have provided information regarding the survival and maintenance of CD4 memory cells, their functional capacities, their differentiation states and program of development following activation. The emerging picture is one of great versatility and functional heterogeneity as befits their central position within the immune system.