Blood represents a reservoir and a migration compartment of cells of the immune system. Traditional microbiologic diagnostic tests relied on laboratory identification of the pathogen causing the infection. However, this approach is less than optimal for a variety of reasons: pathogen's slow growth, resistance to cultivation in vitro or insufficient proof to establish causality when a pathogen is identified. An alternative approach to the pathogen-detection strategy is based on a comprehensive analysis of the host response to the infection by analysis of blood leukocytes gene expression profiles. This strategy has been successfully applied to distinguish and classify children and adults with acute infections caused by different pathogens. Molecular distance to health (MDTH) is a genomic score that measures the global transcriptional perturbation in each individual patient compared to healthy controls. Studies indicate that MDTH is a promising biomarker to help classifying patients according to clinical severity.