Functional genomic technologies such as high density DNA microarrays allow biologists to study the structure and behavior of thousands of genes in a single experiment. One of the fields in which microarrays have had an increasingly important impact is host-pathogen interactions. Early investigations in this area over the past two years not only emphasize the utility of this approach, but also highlight the stereotyped gene expression responses of different host cells to diverse infectious stimuli, and the potential value of broad dataset comparisons in revealing fundamental features of innate immunity. The comparative analysis of recently published datasets involving human gene expression responses to two bacterial respiratory pathogens illustrates many of these points. Comparisons between these large, highly parallel sets of experimental observations also emphasize important technical and experimental design issues as future challenges.