As the genomics era matures, the availability of complete microbial genome sequences is facilitating computational approaches to understand bacterial genomes and DNA structure/function relationships. From the genome of pathogens, we can derive invaluable information on potential targets for new antimicrobial agents. Advancements in high-throughput 'omics' technologies and the availability of multiple isolates of the same species have significantly changed the time frame and scope for identifying novel therapeutic targets. This article aims to discuss selected aspects of the bacterial genome, and advocates 'omics'-based techniques to advance the discovery of new therapeutic targets against extracellular bacterial pathogens.