Biofilm infections involving orthopedic implants are a global problem. They contribute to severe complications and mortality, as well as increased use of antibiotic treatments and development of antibiotic-resistant microorganisms. More than 1 million hip and knee arthroplasties are performed each year in the United States. These hard-to-treat infections lead to patient distress, increased morbidity, and high financial costs to both patients and healthcare systems. There is a need to improve the diagnosis of such biofilm infections to allow for earlier detection and treatment. Current diagnostics rely on clinical signs for infection such as loss of function, fever, rubor, patient history of the predisposing condition, persisting infection, failure of antibiotic treatment, and documentation of antibiotic failure. Below, we present a framework which outlines the data gaps in the conventional laboratory techniques used in clinical diagnostics; we also discuss promising novel diagnostic methods which are currently used solely in research. It is critical to assess these novel infection diagnostic techniques and address the data gaps and the clinical hesitance preventing application in a clinical setting. Additionally, the combination of conventional and novel diagnostic technologies would streamline the diagnostic process of biofilm infections associated with orthopedic implants.