The separation behaviors of four different groups of pharmaceuticals were investigated using cholesteryl-10-undecenoate and ODS phases. The cholesteryl phase, which has liquid crystal properties, showed different selectivity and retention behavior from those of ODS phase. The difference is on its apparent ability to recognize specific structures in the molecules, discriminate among derivatives, or subsequently recognize modifications done on these structures. However, on ODS phase the hydrophobicity effects seem to take precedent as the main factor in its retention mechanism. This enhanced selectivity of the cholesteryl phase is attributed to three contributing structures found in its structure; the long hydrocarbon chain that gives added mobility to the phase, the carbonyl group which can interact with a variety of substituent groups, and the cholesteric moiety which can invoke π-π interaction as well as steric effects. The use of the cholesteryl phase for these kinds of pharmaceutical analyses is therefore warranted and showed interesting possibilities for future applications.