Recent advances in DNA sequencing has made it possible to accurately decipher the entire genetic complement of a probiotic bacterium. Increases in sequencing capabilities have been enhanced through improved computer software that can annotate, or identify, the majority of genes encoded by the sequence. The availability of annotated genome sequence will be important in defining the capabilities of the individual strains of probiotic bacteria. It will also form the platform for microarray and proteomic technologies that allow real-time analysis of RNA and protein expression in the bacterial cell. Investigation of probiotic organisms with these new and potentially powerful tools will facilitate the development of the bacteria as therapeutic agents, and provide the mechanisms to produce advanced probiotic strains. This paper addresses the core technologies in the rapidly growing area of genomics, and their application to the molecular characterisation of probiotic bacteria and host-microbe interactions.