Semiconductor nanoparticles (or quantum dots, QDs) exhibit unique optical and electronic properties such as size-controlled fluorescence, high quantum yields, and stability against photobleaching. These properties allow QDs to be used as optical labels for multiplexed imaging and in drug delivery detection systems. Luminescent silicon QDs and surface-modified silicon QDs have also been developed as potential minimally toxic fluorescent probes for bioapplications. Silicon, a well-known power electronic semiconductor material, is considered an extremely biocompatible material, in particular with respect to blood. This review article summarizes existing knowledge related to and recent research progress made in the methods for synthesizing silicon QDs, as well as their optical properties and surface-modification processes. In addition, drug delivery systems and in vitro and in vivo imaging applications that use silicon QDs are also discussed.