Silicon nanowires (Si NWs) are one of the most important one-dimensional semiconductors, partly due to their ready implementation in modern technology. As sensing applications using Si NWs increase, it is necessary to have well-defined chemical attachment schemes that will provide the desired biomolecular recognition properties, chemical stability, and good interfacial electrical properties. Such surface functionalization will allow the controlled immobilization of biomolecules on Si NWs, which is an important step in designing highly selective and sensitive biosensors. Moreover, such surface modification of Si NWs is not only dedicated to sensing, but is also useful for many other applications (not described in this chapter) such as device integration, controlled cell micropatterning, Si NW internalization, and analyte confinement that is high amount of analytes concentrated in a restricted area to improve their detection by mass spectrometry. Finally, advantages of using photochemistry on Si NWs to either immobilize or release probes are discussed as well as hybrid Si NWs coated with various inorganic materials.