Both high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) techniques should be considered complementary rather than competing, with TLC being used widely in organic synthesis and analytical research. Chiral TLC provides an easy technique for the resolution, isolation, and routine quality control of the enantiomeric purity of active pharmaceutical ingredients and a variety of other racemates, especially for fast and cost-effective analysis with simple equipment. The present chapter describes several approaches in chiral TLC for the separation of amino acids and basic drugs. Analytical approaches for direct enantioseparation include the use of (1) “chiral additive in achiral stationary phase (CAASP),” (2) “chiral mobile-phase additive (CMPA),” (3) “premixing of chiral reagent with the enantiomeric mixture,” and (4) “ligand exchange approach” with copper metal complex. Both pre-coated and custom-prepared TLC plates have been used. (−)-Quinine, (−)-erythromycin, l-(+)-tartaric acid, (S)-naproxen, bovine serum albumin (BSA), and l-amino acids were used as chiral reagents/selectors in different manners for the enantioseparations of (±)-ketamine, (RS)-ketorolac, certain β-adrenergic drugs, and DL-dansyl amino acids, as examples.