This review discusses a fundamental kinetic approach for the modeling of the conversion of complex hydrocarbon mixtures, called single-event approach. Based upon the transition state theory and statistical thermodynamics and combined with the linear free energy relationship of Evans and Polanyi, it significantly reduces the number of independent kinetic parameters. It is applied to the hydrocracking of vacuum gas oil and the methanol-to-olefin process, which is subject to rapid catalyst deactivation by coke formation. The approach considers a detailed composition of the complex feedstocks, made possible by modern analytical techniques and also by recently introduced computerized methods for the molecular reconstruction of oil fractions. The very large reaction networks should be generated by computer and this aspect is also reviewed. Finally, the application of the method of structural contributions in the reduction of the number of independent kinetic parameters of the hydrodesulfurization of oil fractions is also dealt with.