The use of photonic bandgap fibers (PBGF) for biomedical sensing has been demonstrated. The demonstrated PBGF has a blue wavelength shift of 280 nm in the falling photonic bandgap edge (PBE) when the ambient refractive indices inside the holey region change from 1.333 to 1.39, which agrees well with the analytical prediction. Combining this with the knowledge of immobilization techniques and biorecognition elements could open up a new class of PBGF-based label-free biosensors. A sensitivity on the order of 0.1 nmol/L could be achieved by consuming less than 1 microL of sample.