Molecules containing vicinal all-carbon quaternary stereocenters are found in many secondary metabolites, and they exhibit a variety of biological and pharmacological activities. However, the construction of such a structural motif remains a significant challenge in natural product synthesis. Only in recent years have considerable efforts been made to construct vicinal quaternary stereocenters in a single-step operation. In this review, we focus on the different types of methods that have been successfully used in the total synthesis of natural products. Based on the classified reactions for the simultaneous generation of vicinal all-carbon quaternary stereocenters, the total syntheses of the natural products are discussed, placing emphasis on the diastereoselective preparation of vicinal quaternary carbon centers and the subsequent total syntheses.