The separation of enantiomers by open capillary electrochromatography (o-CEC) using Chirasil-Dex as chiral stationary phase (CSP) is reviewed. In Chirasil-Dex, permethylated β-cyclodextrin is linked via a single octamethylene spacer to polydimethylsiloxane. The CSP is coated and thermally immobilized onto the internal surface of a fused-silica column (i.d. 50 μm). Employing a single open-tubular column coated with Chirasil-Dex, a unified enantioselective approach can be realized using the four common chromatographic techniques: o-GC, o-SFC, o-LC and o-CEC. The chiral stationary phase Chirasil-Dex can be combined with a charged cyclodextrin derivative, which is added into the mobile phase. In the resulting dual chiral recognition system, enhancement of enantioselectivity (matched case) or compensation of enantioselectivity (mismatched case) are observed. The overall enantioselectivity is dependent on the sense of enantioselectivity of the selectors chosen and their influence on the electrophoretic and electroosmotic migration of the enantiomers of a selectand. The feasibility to couple chiral o-CEC and ESI/MS is demonstrated for trace analysis of enantiomeric drugs in body fluids.