Abstract: 1,2,4-Triazolo[4,3-a]pyrimidines have significant application prospects in various fields of science, especially as biologically active compounds. This review focused on synthetic approaches of these annulated heterocyclic systems. The main trends, their development, and achievements in this field of synthesis of these classes of heterocyclic compounds, advantages and limitations of the approaches used for 1958–2024 are presented.