This paper first summarizes a new theoretical description that quantifies the effects of real-fluid thermodynamics on liquid fuel injection processes as a function of pressure at typical engine operating conditions. It then focuses on the implications this has on modeling such flows with emphasis on application of the Large Eddy Simulation (LES) technique. The theory explains and quantifies the major differences that occur in the jet dynamics compared to that described by classical spray theory in a manner consistent with experimental observations. In particular, the classical view of spray atomization as an appropriate model at some engine operating conditions is questionable. Instead, non-ideal real-fluid behavior must be taken into account using a multicomponent formulation that applies to hydrocarbon mixtures at high-pressure supercritical conditions. To highlight the implications and needs related to modeling, we present a series of studies using LES that focus on experiments being conducted in the high-pressure combustion vessel at Sandia National Laboratories. We extend LES studies performed previously to the Engine Combustion Network (www.sandia.gov/ECN) Spray-H and Spray-A injectors using n-heptane and n-dodecane as the respective fuels. The accompanying analysis reveals the structural characteristics associated with the inherent scalar mixing processes at conditions directly relevant to advanced Diesel engines.