Multigene families are present on the telomeric and sub-telomeric regions of most chromosomes of the malaria parasite, Plasmodium. The largest gene family identified so far is the Plasmodium interspersed repeat (pir) multigene gene family and is shared by Plasmodium vivax, and simian and rodent malaria species. Most pir genes share a similar structure across the different species; a short first exon, long second exon and a third exon encoding a trans-membrane domain, and some pir genes can be assigned to specific sub-families. Although pir genes can be differentially transcribed in different life cycle stages, suggesting different functions, there is no clear link between sub-family and transcription pattern. Some of the pir genes encode proteins expressed on or near the surface of infected erythrocytes, and therefore could be potential targets of the host's immune response, and involved in antigenic variation and immune evasion. Other functions such as signalling, trafficking and adhesion have been also postulated. The presence of pir in rodent models will allow the investigation of this gene family in vivo and thus their potential as vaccines or in other interventions in human P. vivax infections.