Biosensors utilizing peptide and protein probes offer the potential to provide rapid, highly sensitive, specific, and economical infectious disease diagnostics. In this respect, the following chapter describes recent advances in peptide-based biosensor technologies, including mass perturbance, electrical perturbance, and optical methods. Further, the applicability of these biosensors in the diagnosis of microbial infections in both laboratory and field settings is described. The chapter also discusses current, competing technologies to peptide-based biosensors, as well as point-of-care testing (with an emphasis on the comparison of influenza diagnostics). In addition, the chapter illustrates; 1) the positive impact that rapid diagnosis from biosensors could have on pandemic disease surveillance, 2) describes the different types of peptide-based probes (including antibodies and oligopeptides), and 3) presents an internationally approved clinical method for determining limits of detection for biosensors. The chapter concludes with predictions on the limitations of peptide-based biosensors, and the promising technological advances that will allow full potential of biosensor applications to be achieved within the field of medical microbiological diagnosis.