As the prevalence of resistance to multiple antibiotics increases it is progressively more difficult to treat pneumonia in hospitalized patients. Therefore, anti-infectious agents that have new modes of action are needed urgently. Recent advances in DNA sequencing technology make it possible to elucidate the sequences of the entire genomes of pathogenic bacteria. This allows many novel, non-traditional targets for therapeutic intervention to be identified, such as those involved in disease pathogenesis, and in adaptation and growth at sites of infection. In the past few years, inhibitors of new bacterial targets have been developed, including inhibitors of genes that are required for either virulence or pathogenesis. The challenge is to optimize and develop these agents to provide novel approaches to the treatment of pneumonia in hospitalized patients.