Developing C–H functionalization reactions is a major focus of organic chemistry research. But using different C–H functionalizations sequentially to streamline complex syntheses remains challenging. Houhua Li and Xiaoguang Lei of Peking University and the National Institute of Biological Sciences, both in Beijing, and coworkers have now used an unprecedented four C–H functionalization reactions as part of a 14-step first enantioselective total synthesis of the natural product (–)-incarviatone A (J. Am. Chem. Soc. 2015, DOI: 10.1021/jacs.5b08551). Use of the multiple C–H functionalizations together in one natural product synthesis suggests that C–H functionalization chemistry may be coming of age. (–)-Incarviatone A was isolated in 2012 and found to be a monoamine oxidase inhibitor with potential for treating depression, Alzheimer’s disease, and other neurological disorders. But poor accessibility has deterred further evaluation. The Beijing team used the sequential C–H functionalizations to help assemble the molecule’s functionalized indane skeleton rapidly from a simple phenylacetic acid starting material. “Such a combination of multiple C–H functionalizations can offer previously unthinkable routes for short syntheses of complex molecules,” comments Jin-Quan Yu of Scripps Research Institute California, whose group helped develop some of the C–H functionalization reactions employed in the total synthesis.