Microbial sequencing reveals incorrect assumptions about the origin of certain infections, possibly altering prevention and treatment strategies. Bloodstream infections are a signicant source of morbidity and mortality, especially in hospitalized patients. Certain bloodstream infections in the hospital may be preventable as it is believed that these pathogens are acquired from environmental reservoirs and introduced into patients through catheters. There are no standard methods for assessing the origin of bloodstream pathogens, which can ensure proper treatment. Physicians and hospitals generally rely on historical evidence to determine the pathogen source, tailor treatments, and develop preventive strategies to reduce patient risk of acquiring these infections. Current strategies to assess bloodborne pathogens focus on species identity and antibiotic susceptibility but are insucient for organism tracking, which requires strain level identity. To address this problem, Tamburini et al. combined whole-genome sequencing of pathogen isolates with metagenomic shotgun sequencing of stool samples to track pathogen strains. Patients undergoing hematopoietic stem cell transplant are at high risk for hospital-acquired infections and were sampled as part of a prospective study at Stanford University. Thirty patients were identied with a bloodstream infection during the study and had a stool sample collected prior to the infection. To track bloodstream pathogens, the authors developed a program called StrainSifter. Pathogens were whole-genome sequenced and single-nucleotide variants used to dene the pathogen strain. The authors then used StrainSifter to track pathogen strains in shotgun metagenomic sequencing from samples, such as stool, to determine if this site was a potential reservoir. Using this pipeline, 15 of 32 bloodstream pathogens were identied in stool samples from the corresponding patient. It is thought that abundant gastrointestinal organisms commonly seed the blood, but in this study, the majority of pathogens were present in the stool in low abundance. Interestingly, ve bloodstream pathogens were found in the stool microbiome despite their historical association with the environment (Pseudomonas aeruginosa) and the skin (Staphylococcus epidermidis). The authors conrmed strains were not transmitted between patients and identied antibiotic resistance genes that paralleled in vitro assays. Unfortunately, current gene sequencing and bioinformatics methods are cumbersome and will need faster turnaround before their clinical application. Now physicians and researchers must consider that current strategies to target and treat bloodborne infections may be misguided, and future studies must broadly sample the patient and environmental microbiome to dene pathogen reservoirs and improve outcomes of bloodborne infections.