It is well established that sterile immunity against malaria is hardly ever achieved by natural infection, and that the generation and maintenance of Plasmodium-specific immunological memory wanes in the absence of infection. Although both cell-mediated and antibody-mediated immune responses have been demonstrated to be critical for protection against malaria infection, the underlying mechanisms remain incompletely understood. This PhD thesis aims to address knowledge gaps in our understanding of the development and maintenance of immunological memory to malaria. The main goal of this PhD project is to investigate the induction and maintenance of cellular and humoral immune memory responses to malaria infection. The study utilized 2 approaches. First, using mouse models, I examined the immune responses to acute and chronic blood-stage malaria, with a focus on CD4+ T cells, which play a major role in both cell-mediated and humoral responses against malaria. Plasmodium-specific responses were characterized through CD4+ T cells from T-cell receptor transgenic mice, PbT-II, and analyzed along with other immune cells. The role of the regulatory cytokine IL-27 in the development of immunological memory was investigated. Results showed that early and transient IL-27 inhibition allowed for better PbT-II cell maintenance during chronic infection. Moreover, IL-27 modulation of Th1 memory development had a suppressive effect on the protective capacity of both the cell-mediated and antibody-mediated immunity. Next, through human studies, I determine the effect of differential malaria exposure on immunological memory. Using antibody data from three areas of varying endemicity in the Philippines, I first evaluated different methods of analyzing multiplex serology data. The simultaneous analyses of Plasmodium-specific antibody responses did not only provide accurate estimates of recent and historical malaria exposure, but also provided important implications for the impact of declining transmission on the maintenance of long-lived antibodies and memory cells. A human cohort study protocol is further described with the intention of pursuing further investigation on malaria-specific B and T cell memory responses in areas of varying malaria transmission. Taken together, the findings from this PhD project provided important insights relating to the longevity of immune responses to malaria, contributing relevant information for devising new approaches for interventional and vaccine strategies in the context of malaria elimination.