Cell-free DNA (cfDNA) sequencing has been helpful in diagnosing infectious disease. It allows a pathologist to unbiasly search for all pathogens in a sample instead of culturing for specific ones. However, the presence of contaminant DNA and misidentification of microbes are possible, leading to false-positive diagnoses when using this highly sensitive diagnostic method. A recent study describes a new bioinformatics platform called Low Biomass Background Correction, or LBBC, which searches for and helps remove contaminant DNA from cfDNA samples. In a urinary tract infection screen, LBBC reduced the false positive rate while minimally affecting the true positive rate. And among pregnant women, it allowed researchers to generate a new cfDNA dataset for amniotic fluids. That could help clinicians identify intra-amniotic infection more easily while supporting the view that amniotic fluid is sterile during normal pregnancy. Although it’s important to remember that LBBC may still filter out pathogens of interest, this new tool could make cfDNA sequencing more reliable in detecting pathogens in biological samples.