Pregabalin is a chiral γ-aminobutyric acid analogue, and its synthesis under the principles of green chemistry focuses on step economy, safer reagents, high atom efficiency, and minimal waste generation. One widely discussed and environmentally improved route begins with readily available and less hazardous starting materials and emphasizes asymmetric synthesis to avoid wasteful resolution steps. The process generally starts with the preparation of a substituted alkene or nitrile intermediate derived from simple carbon sources such as isobutyl-containing aldehydes or acids, which are converted under mild conditions using recyclable catalysts. In a green synthetic approach, an initial Knoevenagel-type condensation or alkylation is carried out using benign solvents such as ethanol or water instead of chlorinated solvents. This step forms a carbon–carbon bond efficiently, improving atom economy. The resulting unsaturated intermediate is then subjected to catalytic asymmetric hydrogenation or asymmetric addition using a chiral catalyst, often based on transition metals like rhodium or ruthenium with reusable chiral ligands. This step is crucial, as it introduces the required stereochemistry directly, eliminating the need for classical resolution methods that generate large amounts of unwanted enantiomeric waste. Following stereoselective reduction, the product is converted into a nitrile or