Chiral lanthanide shifts reagents (CLSRs) provide a powerful strategy for distinguishing enantiomers using NMR spectroscopy. In an achiral environment, enantiomers exhibit identical NMR spectra, making their analytical separation challenging. CLSRs resolve this limitation by forming transient diastereomeric complexes with enantiomers, resulting in measurable differences in chemical shift. These reagents typically consist of paramagnetic lanthanide ions coordinated to enantiopure ligands, enabling selective binding through Lewis’s acid–base interactions with functional groups including alcohols, amines, or carbonyls. The paramagnetic nature of the lanthanide center induces strong anisotropic effects, altering the magnetic environment of the bound substrate and enhancing spectral dispersion. This approach supports accurate determination of enantiomeric composition, absolute configuration, and reaction progress in asymmetric synthesis. This chapter discusses the principles, mechanisms, and applications of chiral lanthanide shift reagents in NMR spectroscopy for effective enantiomer discrimination and analysis.