3,3-Disubstituted oxetanes are increasingly important motifs in medicinal chemistry and materials chemistry. Consequently, there has been considerable demand for the development of new synthetic routes toward these valuable scaffolds. This chapter summarizes the most significant recent advances in the synthesis of 3,3-disubstituted oxetanes and their applications in medicinal and energetic materials chemistry. In particular, the reactivity of oxetane building blocks is explored, facilitating their installation as pendant motifs and for late-stage functionalization of complex systems.