The ReaxFF method has been successfully applied to study a wide range of chemistries in the fields of materials and biomolecular science, e.g., hydrocarbons, metal/metal oxides, combustion, catalysis, atomic layer deposition, DNA oxidation, and hydrolysis. In this work, we focus on current and potential future applications of ReaxFF to biological systems using various ReaxFF force field parameterizations specifically developed for the study of common reactive processes in biochemistry, including (1) RNA/DNA cleavage, (2) protonation/deprotonation of imidazole-Zn-ligand complexes, and (3) Cu-catalyzed and noncatalyzed peptide bond hydrolysis. First, ReaxFF reproduced the cleavage mechanism for phosphodiester linkage of RNA and DNA with the atomic level picture. Cleaving RNA yields a 2′-OH,3′-phosphate and a 5′-OH nucleoside via 3′,5′-cyclic phosphate intermediate. Also, due to the absence of a 2′-hydroxyl group in DNA, DNA is cleaved by the nucleophilic attack of water on the phosphorus center, producing a 5′-OH nucleoside and a nucleotide. Second, the interactions between Zn(II) metal and various ligands were successfully compared between ReaxFF and the earlier DFT work, which the ligand dissociation energies and proton affinities are systematically examined in Zn-ligand (L) complexes (L = NH2, NH3, NHCH2, NCH2, and NCH2CH3 functional groups, imidazole, and H2O). Using this force field, we performed a reactive MD simulation for the formation of Zn(Im)n(H2O)m in aqueous at 300 K. The results show that the mixed ligand Zn(Im)n(H2O)m complexes are allowed to have various coordination numbers, due to the dynamic nature of Zn(II) coordination. One of the common and important ligands in metalloprotein is imidazole in a histidine residue. The role of imidazole as a proton donor and acceptor is very essential for the proton transfer occurring at enzyme active sites. We showed that ReaxFF can describe the pH-dependent protonation state of imidazole by investigating the energy barriers for the protonation and performing a reactive MD simulation for the formation of imidazolium cations at low pH. Finally, we compared ReaxFF results for catalyzed and uncatalyzed peptide bond hydrolysis mechanisms. It is found that the transition state is stabilized significantly by the formation of a Cu(II)-complex. The ReaxFF potential energy profiles along the reaction pathway for both catalyzed and uncatalyzed hydrolysis reactions are in excellent agreement with the DFT. The role of imidazole as a bridge for the proton transfer and its biological significance in the Ser-His-Asp catalytic triad were further discussed.