The guided-mode resonance (GMR) sensor operates with resonant leaky Bloch modes induced in periodic films. The resonance occurs in 1D or 2D nanopatterns that are fabricated by nanoimprint technology. Optical sensors are needed in many fields including medical diagnostics and environmental monitoring. Inducing resonance in multiple modes enables extraction of complete bioreaction information including biolayer thickness, biolayer refractive index, and any change in the refractive index in the background buffer solution. We refer to this version of the GMR sensor as the complete biosensor. We summarize the principles, technology, and applications of this basic sensing methodology. As an example application, we use commercial GMR sensors to quantify the detection of peptides. Using a sandwich neuropeptide-Y (NPY) assay, we measure sub-nM NPY concentrations.