Genome scale analyses, comparisons and validations may produce important insights in both basic and applied research: from the understanding of strain physiology and evolution to engineering of metabolic pathways. This chapter described as the availability of genome sequence information can be exploited for the understanding of the biology of the single organism and used in comparative studies with other available genome sequences to gain insights into the taxonomy, phylogeny and evolution of starter and probiotic species. The state of arts of complete genome sequences of potentially probiotic microorganisms is reported, as well as the potential of the metagenomic approach in the delucidation of the microbial flora of the human GI. The development of new, improved and even safer probiotic products, which can be tailor-made to be functional towards specific health conditions, can benefit from the results deriving from advanced nutrigenomics studies.