Pseudomonas aeruginosa is a key opportunistic pathogen causing severe acute and chronic nosocomial infections in immunocompromised or catheterized patients. It is prevalent in burn wound infections and it is generally multi-drug resistant. Understanding the genetic programs underlying infection is essential to develop highly needed new strategies for prevention and therapy. This work reviews expression profiling efforts conducted worldwide towards gaining insights into pathogenesis by P. aeruginosa, in particular in burn wounds. Work on various infection models, including the burned mouse model, has identified several direct virulence factors and elucidated their mode of action. In vivo gene expression experiments using In vivo Expression Technology (IVET) ascertained distinct regulatory circuits and traits that have helped explain P. aeruginosa success as a general pathogen. The sequencing of the whole genome from a number of P. aeruginosa strains and the construction of genome-wide microarrays have paved the road to the several insightful studies on the (interacting) traits underlying infection. A series of in vitro and initial in vivo gene expression studies revealed specific traits pivotal for infection, such as quorum sensing systems, iron acquisition and oxidative stress responses, and toxin production among others. The data sets obtained from global transcriptional profiling provide insights that will be essential for the development of new targets and options for prevention and intervention.