Gasoline is a complex mixture that possesses a quasi-continuous spectrum of hydrocarbon constituents. Surrogate fuels that decrease the chemical and/or physical complexity of gasoline can be used to enhance the understanding of fundamental processes involved in the interaction between fuels and internal combustion engines (ICEs). The aim of this paper is to present methodologies for fuel development and show how surrogate fuels can be used to investigate the effect of individual components and fuel fractions on fuel properties and the performance of commercial engines. For this purpose, experiments were designed and SI engine dynamometer tests were conducted using ten mixtures of iso-octane, toluene, n-heptane and ethanol. Response surface models were statistically developed to analyze the interactions between fuel components, fuel properties and engine performance. It was possible to identify the importance of each component, and its corresponding chemical group, for different engine performance parameters. The methodology implemented can help fuel formulation in general and can be of particular interest for special applications, such as race fuels.