Most of our current knowledge about the gene regulation of pathogen comes from studies with in vitro conditions that mimic their host environments, revealing many types of virulence genes and their regulatory network. Recent advances in DNA sequencing and techniques for transcriptome analysis allow us to identify pathogenic genes specifically expressed in vivo. Analyses for gene expression of pathogens in response to the host environment, including immune response and change of bacterial flora during infection, provide clues to understanding the underlying events to establish the infectious diseases. Here, we would like to introduce next epoch-making ideas and concepts to understand the real picture of microbial infection through the recent works of gene regulation in host environments.