The most important achievements on the synthesis of O- and S-6-membered heterocycles published in 2021 are reviewed. This personal overview is focused on the developments made on the synthesis of a large variety of natural compounds, specific reactions, and reagents for the preparation of natural and synthetic pyrans, chromenes and chromans, isochromenes and isochromans, pyranones, coumarins and isocoumarins, chromones and chromanones, xanthenes and xanthones, thiopyrans and analogues, dioxanes, trioxanes, tetraoxanes, dithiins, and also oxathianes.