Asymmetric catalysis is a direct and efficient method for synthesizing chiral compounds, with its core focus lying in the development of highly efficient chiral catalysts to achieve precise chiral recognition of prochiral faces or prochiral centers in substrates. Although significant progress has been made in this field over the past few decades, most current studies concentrate on substrates containing aryl and alkyl groups, while achieving high enantioselectivity remains challenging when substituents exhibit minimal steric and electronic differences. The precise chiral discrimination of substituents with subtle differences still constitutes a major challenge. In traditional approaches, chiral catalysts primarily rely on steric interactions between the catalyst and substrate to control stereoselectivity, whereas enzymes in nature utilize confined active sites to achieve precise regulation of organic transformations. The recent advances in the precise recognition of minimally diffe- rentiated substrates and their applications in asymmetric catalytic reactions, covering metal catalysis, organocatalysis, biocatalysis, and related areas are summarized.