The need and prospect of incorporating realistic fuel chemistry in large-scale simulations of combustion phenomena and combustor performance utilizing realistic fuels are reviewed. The review first illustrates the intricacies of chemical kinetics in homogeneous and diffusive systems, and emphasizes the essential importance of the comprehensiveness of chemical fidelity for mechanisms at the detailed, reduced, and one-step levels. A systematic approach towards developing detailed reaction mechanisms is then outlined, which is followed by an extensive discussion on the development of reduced mechanisms and the associated strategies towards facilitated computation. Topics covered include skeletal reduction especially through directed relation graph; time-scale analysis and stiffness reduction based on the concepts of quasi-steady species and partial equilibrium reactions, enabled through computational singular perturbation and intrinsic low dimensional manifold; the lumping of isomers and of species with similar diffusivities; on-the-fly stiffness removal; the relative merits of implicit versus explicit solvers; and computation cost minimization achieved through tabulation and the judicious re-sequencing of the computational steps in arithmetic evaluations. Examples are given for laminar and DNS turbulent combustion to demonstrate the utility of the component methods and the integrated strategy for large fuels whose detailed mechanisms consist of hundreds of species and thousands of reactions. Directions for further research are suggested.