In sensitivity-based finite element model updating, the eigensolutions and eigensensitivities are calculated repeatedly, which is a time-consuming process for large-scale structures. In this chapter, a forward substructuring method and an inverse substructuring method are proposed to fulfill the model updating of large-scale structures. In the forward substructuring method, the analytical FE model of the global structure is divided into several independent substructures. The eigensolutions of each independent substructure are used to recover the eigensolutions and eigensensitivities of the global structure. Consequently, only some specific substructures are reanalyzed in model updating and assembled with other untouched substructures to recover the eigensolutions and eigensensitivities of the global structure. In the inverse substructuring method, the experimental modal data of the global structure are disassembled into substructural flexibility. Afterwards, each substructure is treated as an independent structure to reproduce its flexibility through a model-updating process. Employing the substructuring method, the model updating of a substructure can be conducted by measuring the local area of the concerned substructure solely. Finally, application of the proposed methods to a laboratory tested frame structure reveals that the forward and inverse substructuring methods are effective in model updating and damage identification.