This chapter aims to give some insights into supercritical fluid (SCF) applications in reaction systems in view of chemical engineering applications. In chemical reactions, the reaction medium is usually a fluid solvent that must have specific characteristics that can be regulated through temperature and pressure of the system to above its critical point. The supercritical technology can favorably modify the solvent properties as required for reactions. Some applications of SCFs and specifically supercritical water (SCW) are discussed in this chapter including waste destruction, biomass processing, and chemical synthesis. Furthermore, important factors influencing SCF-biocatalytic reaction systems (enzyme-catalyzed reactions) including the effect of water content on enzyme operation in the presence of SCFs, the effect of operation conditions, and the effect of solvent characteristics are also elaborated. A discussion on the challenges and limitations of SCFs for industrial applications is also provided. © 2021 Elsevier Inc. All rights reserved.