Raman spectra are molecule specific, and their peaks in the fingerprint region (200-2000 cm−1) are often sufficient for material identification. High-wavenumber signals (> 2000 cm−1) are rare in inorganic material but rich in organic materials containing light hydrogen atoms. Reports on high-wavenumber (HW) Raman signals are far less than fingerprint signals. This could be partially attributed to the difficulty obtaining HW Raman signals, especially from biological materials containing fluorescent proteins. The development and the availability of InGaAs array and the near-infrared (NIR) laser enabled the acquisition of distinct HW Raman from bio-materials. In this chapter, we will introduce recent applications of HW Raman spectroscopy on different materials, especially on biological tissues. Raman instrumentation based on multiple lasers or multiple spectrometers will also be discussed.