Both eukaryotic and prokaryotic pathogens infect the host stably via an immune evasion mechanism termed mutually exclusive expression.Nowadays,little is known about this epigenetic mechanism,largely limiting the understanding of pathogenesis of many bacterial,fungal and protozoan pathogens and therefore the development of novel drugs and vaccines.In the most severe malaria parasite,Plasmodium falciparum,there is a major virulence gene family termed var,by which the variant antigen PfEMP1 is encoded and expressed on the surface of parasite-infected erythrocytes.Each parasite carries about 60 antigenically various var genes,however,only one of which is expressed at a given time during infection.P.falciparum expresses PfEMP1 s in this clonally variant manner to bind to different human endothelial receptors,allowing the infected erythrocytes to sequester in tissues to escape the host’s immune response including spleen killing and humoral immunity.At present,the mechanism of mutually exclusive expression of the var gene family remains largely unknown,even though there is increasing evidence suggesting important roles of the epigenetic regulation involved in var gene expression.In addition,epigenetic factors were also found in association with transcriptional regulation of other antigenic variant gene families in P.falciparum.In this paper,we review the current understanding of epigenetic regulations of P.falciparum virulence genes with particular views toward the design of novel vaccines,drugs,and diagnosis to malaria. Both eukaryotic and prokaryotic pathogens infect the host stably via an immune evasion mechanism termed mutually exclusive expression. Nowadays, little is known about this epigenetic mechanism, largely limiting the understanding of pathogenesis of many bacterial, fungal and protozoan pathogens and therefore the development of novel drugs and vaccines. In the most severe malaria parasite, Plasmodium falciparum, there is a major virulence gene family termed var, by which the variant antigen PfEMP1 is encoded and expressed on the surface of parasite-infected erythrocytes. Each parasite carries about 60 antigenically various var genes, however, only one of which is expressed at a given time during infection. P.. falciparum expresses PfEMP1 s in this clonally variant manner to bind to different human endothelial receptors, allowing the infected erythrocytes to sequester in tissues to escape the host’s immune response including spleen killing and humoral immunity. At present, the mechanism of mutually exclus ive expression of the var gene family remains substantially unknown, even though there is increasing evidence suggesting important roles of the epigenetic regulation involved in var gene expression. In addition, epigenetic factors were also found in association with transcriptional regulation of other antigenic variant gene families in P. falciparum. This paper, we review the current understanding of epigenetic regulations of P. falciparum virulence genes with particular views toward the design of novel vaccines, drugs, and diagnosis to malaria.