In the last decade, the field of nanoparticle (NP) technology has attracted immense interest in bioimaging and biosensing research. This technology has demonstrated its capability in obtaining sensitive data in a noninvasive manner, promising a breakthrough in early-stage cancer diagnosis, stem cell tracking, drug delivery, pathogen detection and gene delivery in the near future. However, successful and wide application of this technology relies greatly on robust NP engineering and synthesis methodologies. The NP development steps involve design, synthesis, surface modification and bioconjugation. Each of these steps is critical in determining the overall performance of NPs. It is desirable to obtain NPs that are highly sensitive, stable, imageable, biocompatible and targetable. It is also desirable to obtain multimodal/multifunctional NPs that will enable imaging/sensing of the target using multiple imaging/sensing modalities. In this review, we focus on silica NPs that have been developed for biosensing applications and silica-based multimodal/multifunctional NPs for bioimaging applications.