During the golden age of antibiotic discovery, from the 1930s through the 1960s, methods of antibiotic identification relied solely on scientific observation, and while chemical analogues such as amoxicillin, derived from penicillin, continued to be developed, they retained the same mechanisms of action and hence the same bacterial targets. Moreover, there are finite modifications that can ultimately be made to "old" classes of antibiotics. Consequently, only two new classes of antibiotics have been discovered in the past 40 years, and both entered the market early in the new millennium. The advent of the genomics revolution offered a new hope for the discovery of novel antimicrobial targets. Genomic strategies were utilized to identify potential antibacterial targets, namely those that, if inhibited, resulted in the death of the bacterium. Such targets were to be present in pathogenic strains of bacteria and absent from the human host; they could include metabolic pathways, receptor ligands, and virulence traits, to name a few. Despite the abundance of targets identified using this strategy, no new antibiotics have reached the marketplace as a result of the genomics approach. However, new antimicrobials with novel targets continue to be identified and contribute to the ongoing struggle against antimicrobial resistance that threatens to return humankind to a situation comparable to the preantibiotic era.