The recent advent of genomic approaches for association testing is starting to enable a more comprehensive understanding of the role of human immune response in determining infectious disease outcomes. Progressing from traditional linkage approaches using microsatellite markers to high-resolution genome-wide association scans, these new approaches are leading to the robust discovery of a large number of disease susceptibility genes and the beginnings of an appreciation of their connections. In this commentary, we discuss how this technology development has led to increasingly complex and common infectious diseases being unraveled, and how this is starting to dissect pathogen-specific human responses. Intriguingly, these still preliminary findings suggest that pathogen innate detection mechanisms may not be as shared among diseases as immune response mechanisms.