Advanced microbiology technologies are rapidly changing our ability to diagnose infections, improve patient care, and enhance clinical workflow. These tools are increasing the breadth, depth, and speed of diagnostic data generated per patient, and testing is being moved closer to the patient through rapid diagnostic technologies, including point-of-care (POC) technologies. While select stakeholders have an appreciation of the value/importance of improvements in the microbial diagnostic field, there remains a disconnect between clinicians and some payers and hospital administrators in terms of understanding the potential clinical utility of these novel technologies. Therefore, a key challenge for the clinical microbiology community is to clearly articulate the value proposition of these technologies to encourage payers to cover and hospitals to adopt advanced microbiology tests. Specific guidance on how to define and demonstrate clinical utility would be valuable. Addressing this challenge will require alignment on this topic, not just by microbiologists but also by primary care and emergency room (ER) physicians, infectious disease specialists, pharmacists, hospital administrators, and government entities with an interest in public health. In this article, we discuss how to best conduct clinical studies to demonstrate and communicate clinical utility to payers and to set reasonable expectations for what diagnostic manufacturers should be required to demonstrate to support reimbursement from commercial payers and utilization by hospital systems.