question: Children suffering from infectious diseases, both bacterial and viral, are often treated with empirical antibiotics. Keeping in mind both the menace of microorganisms and antibiotic toxicity, it is imperative to develop point-of-care testing (POCT) to discriminate bacterial from viral infections, and to define indications for antibiotic treatment. This article reviews potential protein biomarkers and host-derived gene expression signatures for differentiating between bacterial and viral infections in children, and focuses on emerging multiplex POCT devices for the simultaneous detection of sets of protein biomarkers or streamlined gene expression signatures that may provide rapid and cost-effective pathogen-discriminating tools.