Plasmodium falciparum infections have been implicated in immune deficiencies resulting in ineffective control of Epstein-Barr virus, thereby increasing the risk of endemic Burkitt lymphoma in children. However, the impact of Epstein-Barr virus infections on the development of immunity to P. falciparum has not been studied in depth. In this review, we examine novel findings from animal co-infection models and human immuno-epidemiologic studies to speculate on the impact of acute gammaherpesvirus co-infection on malarial disease severity. Children are often concurrently or sequentially infected with multiple pathogens, and this has implications for understanding the development of protective immunity as well as in the evaluation of vaccine efficacy.