Peptide bonds, the amide bonds formed between α-amino acids, constitute the backbone of peptides and proteins. Although peptide bonds can be constructed efficiently under mild reaction conditions in nature, their chemical approach imposes great challenges on chemists. The notorious racemization/epimerization issue caused by the “overactivation” of the carboxylic groups by using conventional coupling reagents always complicated peptide synthesis and purification. Alternatively, active esters with well-defined structures and moderate reactivity, formed in situ or prior prepared, play a crucial role in suppressing racemization/epimerization. Herein, we systematically and critically summarized the pros and cons of using active esters in peptide syntheses with a hope of stimulating novel innovations for disruptive peptide synthesis strategies.