Building block-approach is one of the basic strategies used by nature in biogenetic synthesis. Naturally occurring L-α-amino acids, L-α-hydroxy acids, D-mono-sugars, and terpenes, being cheap and easily available in enantiopure forms, have found widespread applications enantioselective synthesis as chiral building blocks. L-Malic acid, an L-α-hydroxy diacid, is a readily available and cheap natural chiron, D-malic acid is also commercially available although it is more expensive. With all of the four carbon atoms transformable or functionalizable, malic acid serves as a versatile C₄ building block in organic synthesis for enantioselective synthesis. In this review, the progress in the applications of malic acid in organic synthesis is summarized. Firstly, the transformations of malic acid into a variety of advanced chiral C₄ building blocks are compiled. Secondly, selected examples on the applications of these versatile intermediates in the total synthesis of complex natural products in recent years are presented. Besides, the developments of malic acid-based new synthetic methodologies including the contribution from one of the authors’ laboratory are highlighted. An outlook for future development of malic acid-based synthetic strategy is provided.