In this work, the synthesis of oxazolo[4,5-d]pyrimidines and oxazolo[5,4-d]pyrimidines is reviewed. The review is focused on the construction of the scaffold rather than on its further modification. Nevertheless, selected examples illustrate some of the most common modifications of these scaffolds. The synthetic part is complemented by an overview of their biological activity. This review covers literature and patents from 1967 until the present.