Abstract Internal combustion engines running on liquid fuels will remain the dominant prime movers for road and air transportation for decades, probably for most of this century. The world’s appetite for liquid transportation fuels derived from petroleum and other fossil resources is already immense, will grow, will at some future time become economically unsustainable, and will become infeasible only in the very long term. The ongoing process of augmenting and eventually replacing petroleum-derived fuels with liquid alternative fuels must necessarily involve approaches that result in comparatively much lower net carbon cycle emissions from the transportation sector, most likely through a combination of carbon sequestration and renewable fuel production. The successful growth and establishment of a sustainable, profitable alternative fuels industry will be best facilitated by approaches that integrate alternative products into petroleum-derived fuel streams (i.e., gasolines, diesel, and jet fuels) and consider synergistic evolution of and integration with prevailing refining and liquid fuel distribution infrastructures. The emergence of low temperature combustion strategies, particularly those implementing dual fuel methods to achieve Reaction Controlled Compression Ignition (RCCI), offers the potential to significantly improve operating efficiency and reduce emissions with minimal aftertreatment. For all advanced combustion engine technologies, but especially for RCCI, a clear understanding of fuel property influences on combustion behaviors will be important to achieving projected engine performance and emissions. To achieve the benefits projected by emerging engine technologies, the properties of petroleum-derived fuels themselves must be modified over time, but the effects of blending candidate alternative fuels with these conventional fuels must also be understood. Predicting the coupled physical and chemical property effects of real fuels on energy conversion system performance and emissions is a daunting problem, even for petroleum-derived real fuels, since each is composed of several hundred to thousands of individual chemical species typically belonging to one of a few organic classes (e.g., n-paraffins, iso-paraffins, cyclo-paraffins, olefins, aromatics). For specific combustion applications, it is often the global combustion response to variations in the composition of fuel mixtures – inclusive of those occurring by blending petroleum-derived fuel with alternative fuel candidates – that is of interest for fuel property optimization. This paper presents an overview of tools used for evaluating and emulating combustion-relevant properties of real fuels and alternative fuel candidates. New analytical and statistical methods can provide important insights as to how the ensembles of distinct molecular structures found in a given fuel mixture contribute to the physical and chemical kinetic properties that govern its combustion in energy conversion processes. Such tools can in turn assist in screening candidate alternative fuels for more detailed study.