Porous silicon waveguide biosensors that utilize grating couplers etched directly into porous silicon are demonstrated for improved molecular detection capabilities. Molecules are infiltrated through the grating couplers into the waveguide where they can interact with a guided waveguide mode. Hybridization of nucleic acids inside the waveguide is shown to significantly perturb the wave vector of the guided mode and is detected through angle-resolved reflectance measurements. A detection sensitivity of 7.3°/mM is demonstrated with selectivity better than 6:1 compared to mismatched sequences. Experimental results are in good agreement with calculations based on rigorous coupled wave analysis. Use of the all-porous silicon grating-coupled waveguide allows improved interaction of the optical field with surface-bound molecules compared to evanescent wave-based biosensors.