Chiral discrimination by NMR spectroscopy has traditionally relied on 1H NMR because of its high abundance and sensitivity. However, 1H NMR often produces crowded spectra with complex multiplets and limited chemical shift separation, reducing its effectiveness for distinguishing enantiomers. To overcome these limitations, 19F NMR has emerged as a powerful alternative. The 19F nucleus provides a broad chemical shift range, simpler coupling patterns, and minimal background signals, making it highly suitable for stereochemical analysis particularly when fluorinated chiral derivatizing or solvating agents are used. This chapter summarizes current methods and advances in 19F NMR-based chiral discrimination. It highlights key design principles for fluorinated chiral auxiliaries and presents representative applications demonstrating improved analytical clarity.