Purpose of review Gastrointestinal pathogens profoundly affect human health and well being. The provider's ability to render optimal care often highly depends on diagnostic microbiologic support. We aim to provide a clinically pertinent assessment of the current state of our ability to diagnose human gastrointestinal pathogens and describe (and decry) the unsophistication of many current diagnostic methods and strategies. Recent findings Recent advances involve improved stool polymerase chain reaction assays and application of this technology to a broader panel of pathogens, stool antigen assays, and improved culture techniques, but there is little penetration of such diagnostic advances into clinical practice. Many such techniques remain limited to research or epidemiologic use and are not typically available in the clinical laboratory. Summary Multiple clinical and laboratory factors need to be considered when attempting to diagnose the wide variety of gastrointestinal pathogens afflicting humans. Careful interpretation of diagnostic tests with attention to the population studied and the characteristics of each test is necessary.