This article describes strategies for achieving fluorescence enhancement in optical biochips. Two strategies are discussed: plasmonic enhancement, which is due to the localized surface plasmon resonance of metal nanostructures that are adjacent to the fluorescent labels in optical immunoassays; and the use of high-brightness silica nanoparticles as enhanced labels. We present a review of the state-of-the-art in both areas, including synthesis techniques for the metal and silica nanoparticles and the use of the nanoparticles in optical immunoassays. Data are presented that highlight the key design parameters which influence the level of enhancement and model assay data are presented that illustrate potential enhancements in assay performance.