Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important virulence factor encoded by a family of roughly 60 var genes and is used by the parasite to interact with the human host. The parasite regularly exchanges the expressed var gene generating antigenic variation of the infected RBCs (pRBC) surface which is crucial for successful proliferation and transmission. PfEMP1 is also an adhesive molecule that binds to an array of human receptors. By sequestration in the post-capillary venules, pRBCs are able to escape the spleen-mediated clearance but severe malaria may develop if the local binding is extensive. Anti-PfEMP1 immunity is important for preventing the development of both cerebral malaria and placental malaria, but more immunological studies on PfEMP1 antigens and their interaction with the human host are needed. Over the last few years our knowledge about var genes and PfEMP1s has increased dramatically through genetic, biochemical, immunological and epidemiological studies. In addition, the genome sequence has also provided us with a new platform for further dissecting its biological functions. This review highlights the recent analyses of var genes in the P. falciparum genome and postulates significance of genome recombination to the diversity of parasite virulence.