Thousands of pathogens are known to infect humans, but only a fraction are readily identifiable using existing diagnostic methods. Microbial cell-free DNA sequencing offers the potential to non-invasively identify pathogens causing infection throughout the body, but several challenges to producing a clinical-grade metagenomics test had to be overcome. Here we describe the development and performance of the Karius Test, an infectious disease diagnostic test that uses microbial cell-free DNA in plasma to non-invasively identify infecting pathogens. We will present clinical study results evaluating the accuracy and utility of the Karius Test across a variety of patient types.