In this talk,I will present our recent progresses in developing electronic structure methods for large systems and provide some interesting applications of these methods.For large molecules,we have developed two types of approaches for ab initio calculations of very large molecules.One approach is the “cluster-in-molecule”(CIM)approach for local electron correlation calculations based on orthonormal localized molecular orbitals(LMOs).1-2 For this approach,we have recently proposed a new strategy for building clusters to further improve its accuracy.3,4 This progress allows the CIM method to become a reliable and efficient method for electron correlation calculations of very large systems.Another approach is the generalized energy-based fragmentation(GEBF)approach,in which the ground-state energy of a large molecule can be extracted directly from energies of various “embedded” subsystems.5 The GEBF approach can be used to obtain relative energies of different conformers,optimized structures,vibrational spectra,and some molecular properties for many complex systems of chemical interest.6-9 Very recently,we have extended the GEBF approach to molecular crystals with periodic boundary conditions.10 Furthermore,the energy gradients of the GEBF approach for both atom coordinates and translation vectors have been implemented so that the method is applicable for optimizing the crystal structure.Combined with explicitly correlated coupled cluster theory,the GEBF-CCSD(T)-F12 approach has been applied to a series of molecular crystals and the prediction of lattice energies are in excellent agreement with experiment data.The GEBF method is expected to become a promising tool for studying molecular crystals and other solid-state systems.