Cross-coupling reactions are powerful synthetic tools to construct diverse chemical bonds often found in, for example, advanced materials and pharmaceuticals. Since their discovery, haloarenes have habitually been used as electrophilic coupling partners both in academic and industrial contexts. However, concerning the efficiency and the often-negative environmental impact of haloarene-based cross-coupling processes, more readily available, inexpensive, and environmentally friendly electrophiles have been explored.Nitroarenes, for example, are obtained from the facile nitration of aromatic compounds and, thus, represent one of the most easy-to-access feedstock electrophiles. Furthermore, their electron-deficient arene core can be functionalized easily and site-selectively through a wide variety of reactions. Yet, despite these advantages and even though the direct transformation of the NO2 group would be an attractive option in cross-coupling chemistry, it has so far remained difficult to convert nitroarenes via a cleavage of the Ar-NO2 bond given the inherent reactivity (or the lack thereof) of the nitro group. Such denitrative conversion has been performed by a conventional sequence of reduction, diazotization, and Sandmeyer reactions, which severely lacks efficiency and generality.This Account summarizes our recent research progress on cross-coupling reactions that employ nitroarenes as electrophiles. First, we developed the Suzuki-Miyaura coupling of nitroarenes using a palladium/BrettPhos catalyst. This reaction proceeds via an (at the time) unprecedented oxidative addition of the Ar-NO2 bond, which was supported by experimental results and theoretical calculations. A widely accepted catalytic cycle for Pd-catalyzed cross-couplings has since been extended to include nitroarenes as electrophiles, which significantly increases substrate generality. Second, this denitrative coupling protocol was applied to various bond-forming reactions, namely, Buchwald-Hartwig amination, etherification, and hydrogenation reactions. Such diversification has enhanced the utility of nitroarenes as cross-coupling partners. To develop each reaction, it was necessary to modify the reaction conditions as required to overcome the obstacles deriving from nitro functionality including transmetalation and side reactions, as well as oxidative addition. Third, we designed a new Pd/NHC catalyst that exhibits higher activity than Pd/BrettPhos. The improved performance of Pd/NHC system was supported by its strong electron-donicity and structural robustness, and it allows the reduction of the catalyst loading significantly, thus increasing the efficacy and practicality of this method.The field of nitroarene-based cross-coupling has just started to flourish. In addition to our original work, several research groups have already adopted Pd/BrettPhos or Pd/NHC catalysts to develop new denitrative functionalizations. The utility of nitroarenes in the context of organic synthesis should be now revisited.