This research describes the potential to adopt detailed chemical kinetics for practical and potential future fuels using tri-component surrogate mixtures capable of simulating fuel octane “sensitivity” . Since the combustion characteristics of modern fuels are routinely measured using the RON and MON of the fuel, a methodology to generate detailed chemical kinetic mechanisms for these fuels based on these data is presented. Firstly, a novel correlation between various tri-component blends (comprised of i-octane, n-heptane and toluene) and fuel RON and MON was obtained by carrying out standard octane tests. Secondly, a chemical kinetic mechanism for tri-component fuels was validated using a Stochastic Reactor Model (SRM) suite, an in-cylinder engine combustion simulator, and a series of engine experiments conducted in HCCI operating mode. Thirdly, the methodology was applied to predict combustion characteristics of a practical gasoline and fuel blends with ethanol and di-iso-butylene blends using detailed chemical kinetics. Finally, for the first time the application of this technique was demonstrated by employing detailed chemistry in the optimization of two engines and two fuels operating in HCCI mode. Here a parametric study highlighted the adoption of fuels with “sensitivity” could significantly extend the HCCI peak operating IMEP limit by as much as 60%.