Practical syntheses of natural products and their analogues with eight-membered carbocyclic skeletons are important for medicinal and biological investigations. However, methods and strategies to construct the eight-membered carbocycles are limited. Therefore, developing new methods to synthesize the eight-membered carbocycles is highly desired. In this Account, we describe our development of three rhodium-catalyzed cycloadditions for the construction of the eight-membered carbocycles, which have great potential in addressing the challenges in the synthesis of medium-sized ring systems. The first reaction described in this Account is our computationally designed rhodium-catalyzed two-component 5 + 2 + 1 cycloaddition of ene–vinylcyclopropanes (ene–VCPs) and CO for the diastereoselective construction of bi- and tricyclic cyclooctenones. The design of this reaction is based on the hypothesis that the C­(sp3)–C­(sp3) reductive elimination of the eight-membered rhodacycle intermediate generated from the rhodium-catalyzed cyclopropane cleavage and alkene insertion, giving Wender’s 5 + 2 cycloadduct, is not easy. Under CO atmosphere, CO insertion may occur rapidly, converting the eight-membered rhodacycle into a nine-membered rhodacycle, which then undergoes an easy C­(sp2)–C­(sp3) reductive elimination process and furnishes the 5 + 2 + 1 product. This hypothesis was supported by our preliminary DFT studies and also served as inspiration for the development of two 7 + 1 cycloadditions: the 7 + 1 cycloaddition of buta-1,3-dienylcyclopropanes (BDCPs) and CO for the construction of cyclooctadienones, and the benzo/7 + 1 cycloaddition of cyclopropyl-benzocyclobutenes (CP-BCBs) and CO to synthesize the benzocyclooctenones. The efficiency of these rhodium-catalyzed cycloadditions can be revealed by the application in natural product synthesis. Two eight-membered ring-containing natural products, (±)-asterisca-3(15),6-diene and (+)-asteriscanolide, have been synthesized using the 5 + 2 + 1 cycloaddition as the key step. In the latter case, excellent asymmetric induction was obtained using a chiral substrate. The efficiency of the 5 + 2 + 1 reaction was further demonstrated by the synthesis of four sesquiterpene natural products, (±)-pentalenene, (+)-hirsutene, (±)-1-desoxyhypnophilin, and (±)-hirsutic acid C, containing linear or branched triquinane skeletons utilizing the tandem or stepwise 5 + 2 + 1 cycloaddition/aldol reaction strategy. With the success of 5 + 2 + 1 cycloaddition in natural product synthesis, application of the 7 + 1 and benzo/7 + 1 cycloadditions in target- and function-oriented syntheses can be envisioned.