The majority of enantiomeric separations for purity analysis and quality control continue to be performed by liquid chromatography (LC). However, the trend in preparative scale chromatography is rapidly moving the emphasis to supercritical fluid chromatography (SFC) to reduce raw material, processing and waste costs. Fortunately for the analytical chemist, the same stationary phases are used for both normal phase LC and SFC. Analytical laboratories must be ready to continually address the changing nature of molecules in development in the pharmaceutical industry. In our laboratory, preliminary data analysis of chiral screening strategies indicated that the analytical chromatography results from the SFC runs were as superior to the liquid chromatographic results. Using polysaccharide based stationary phases (Diacel AD, OD, AS, and OJ), SFC apparently produced better selectivity than LC screening systems using the same columns and samples. Both were normal phase techniques. And, while SFC mobile phases present several chromatographic advantages, selectivity should not be one of them. A follow up investigation was initiated to look further into this apparent incongruity. The chromatographic results presented illustrate that the difference resulted from the modifiers used rather than from the chromatographic mode used (liquid versus supercritical fluid).