2,5-Dihydro-1,3,4-oxadiazoles with heteroatom substituents at C-2 (also known as corresponding Δ3-1,3,4-oxadiazolines) are very useful materials for the thermal generation of acetoxy(alkoxy)-, dialkoxy-, alkoxy(aryloxy)-, diaryloxy-, alkoxy(alkylthio)-, bis(alkylthio)- and alkoxy(amino)-carbenes. Such carbenes are relatively nucleophilic and react with a variety of electrophilic functional groups. This Account reviews our work to prepare 2,5-dihydro-1,3,4-oxadiazoles and apply them to the synthesis of other target molecules. Carbenes bearing alkoxy substituents at the carbene carbon can be looked upon as acetals of carbon monoxide. Their reactions with electron-deficient alkenes or alkynes can afford acetals of cyclopropanones or cyclopropenones. Although such products may be formed by concerted cycloaddition, initial formation of one bond to produce zwitterions is likely in some cases. In addition, the reactions of these molecules with carbonyl compounds could involve acetals of α-lactones as intermediates. Although we have isolated some acetals of cyclopropanones, we have not isolated the other intermediates. However, some of the products we observe probably resulted from these intermediates. For example, dimethoxycarbene reacts with maleic anhydrides to generate six-membered rings by apparent carbonyl addition followed by an acyloxy group transfer. Similarly, dimethoxycarbene reacts with thiocarbonyl compounds, such as xanthates, by apparent carbonyl addition and transfer of the alkylthiyl group to the erstwhile carbene carbon. Reaction of ROC:(OR)′ with an alcohol R′′OH or a phenol should generate chiral (racemic) orthoformates. Similarly, reaction of alkoxy(alkylthiyl) carbenes with alcohols could generate chiral (racemic) dialkyl thiyl orthoformates. 2,5-Dihydro-1,3,4-oxadiazoles are particularly useful for synthetic applications because they are easily prepared and reasonably stable, thermal sources of bis(heteroatom)carbenes. Such carbenes react with a variety of electrophilic functional groups, often with rearrangement of initial products. Those products, many of them new, could be used as starting materials toward other synthetic targets. Isolation of products from the reaction is relatively simple because the coproducts of thermolysis of the oxadiazoles are primarily N2 and a ketone, such as acetone. Thus, 2,5-dihydro-1,3,4-oxadiazoles should be part of every synthesis chemist’s toolbox.