Water buffalo were domesticated over 5,000 years ago. There are two types of domestic buffalo: River Buffalo (Bubalus bubalis) found in the west, and Swamp Buffalo (Bubalus carabanesis) found from India to the Philippines. The buffalo genome project has three components: 1) de novo sequencing, assembly, annotation, and transcriptome analysis, 2) variation analysis and the creation of a SNP panel, and 3) comparative sequencing of river, swamp and other buffalo species. Sequence information has been produced for the Mediterranean buffalo genome from Illumina and 454 sequence: over 900M Illumina reads, of which about 35% were 5K jump libraries, and 13M 454 reads, of which about 30% were mate pair. The total clone coverage was more than 40X. The sequence assembly is ongoing using the MSR-CA software of UMD. Annotation will be supported by RNA-seq data which has been produced from 31 tissues, giving over 700M reads. Variation discovery is in progress by sequencing samples from different breeds of river and swamp buffalo. We invite the international research community to participate in the study of structural and function variations among the buffalo and related species genomes.