Whispering gallery mode (WGM) resonators are optical cavities with extremely high sensitivity for detecting minute changes in the resonator’s surrounding environment. Enabled by strong optical confinement and long photon lifetimes, WGM resonators allow unlabeled detection of biomolecules such as proteins and nucleic acids, and have the potential to become powerful tools in fundamental biological research. At present, however, technical noise inherent in WGM biosensing experiments constrains their operation to sensitivities many orders of magnitude worse than the fundamental limit determined by quantum shot noise. In this thesis, we propose and develop two avenues for enhancing the sensitivity of WGM biosensors. The first is based on direct detection of the light back-scattered by binding molecules. In principle, the technique is immune to laser frequency noise, and we demonstrate 27 dB of frequency noise suppression using an AFM tip to simulate the presence of a biomolecule. The second technique utilizes electric field hot-spots created by plasmonic nanoparticles deposited on the resonator surface. We show through numerical modeling that these plasmonic nanoparticles could lead to large enhancements in sensitivity, potentially enabling single molecule detection and measurement of conformational changes within molecules under practical experimental conditions. We also show experimentally that the well-known Pound-Drever-Hall frequency locking technique can be employed for detecting plasmonic nanoparticles in real-time, with improved time resolution over existing techniques. In addition, we show that the deposition of plasmonic nanoparticles can strongly couple WGMs within the resonator leading to effects similar to electromagnetically induced transparency (EIT) in atomic systems, which could further enhance measurement sensitivities in sensing nanoscale objects. Lastly, we show that tapered nanofibers, the input coupler which is often used to excite WGM resonators, can be used to detect and trap nanoparticles with high sensitivity, and we explore the possibility of single molecule sensing using tapered nanofibers.