Ephedrine and pseudoephedrine (ψ-ephedrine), frequently found in packaged drugs of abuse, are common over-the-counter pharmaceuticals. Present in high concentrations, these compounds have reportedly caused false identification of methamphetamine in urine specimens. Furthermore, (−)-ephedrine and (+)-ψ-ephedrine are used for manufacturing (+)-methamphetamine. Thus, knowledge on the enantiomeric compositions of these compounds may help identify their sources, providing valuable information to the investigation process. High pressure liquid chromatography (HPLC) and capillary electrophoresis (CE) methods were evaluated and compared for their application in analyzing the enantiomeric compositions of these two compounds. A chiral column (Supelcosil LC-(S) Naphthyl Urea) was found effective in resolving the resulting four components when derivatized with both of the following two chiral derivatization reagents: N-trifluoroacetyl-l-prolyl chloride (l-TPC) and 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl isothiocyanate (GITC). A C18 column, although less effective, can also adequately resolve these four components for identification purposes. With CE, inclusion of 30 mM hydroxypropyl-β-cyclodextrin in 50 mM phosphate buffer (pH 2.5) was very effective in resolving all four components using an uncoated fused silica capillary without prior derivatization.