Effective solutions to antibacterial resistance are among the key unmet medical needs driving the antibacterial industry. A major thrust in a number of companies is the development of agents with new modes of action in order to bypass the increasing emergence of antibacterial resistance. However, few antibacterials marketed in the last 30 years have novel modes of action. Most recently, genomics and target-based screening technologies have been emphasized as a means to facilitate this and expedite the antibacterial discovery process. And although no new antibacterials have yet been marketed as result of these technologies, genomics has delivered well-validated novel bacterial targets as well as a host of genetic approaches to support the antibacterial discovery process. Likewise, high throughput screening technologies have delivered the capacity to perform robust screenings of large compound collections to identify target inhibitors for lead generation. One of the principal challenges still facing antibacterial discovery is to become proficient at optimizing target inhibitors into broad-spectrum antibacterials with appropriate in vivo properties. Genomics-based technologies clearly have the potential for additional application throughout the discovery process especially in the areas of structural biology and safety assessment.