The selective functionalisation of C–H bonds is a powerful strategy for the construction of organic molecules and the Rh(II)-catalysed C–H insertion reaction is a particularly robust and useful tool for this purpose. This review discusses the insertion of Rh(II) carbenes into C–H bonds that are activated by α-oxygen substituents, focusing on the trends that have been observed in reactivity and selectivity, and the applications of this reaction to the total synthesis of complex natural products.